Adenocarcinoma, Neoplasms
Conditions
Keywords
Pediatric Tumors
Brief summary
This is an open label, two-part study of temsirolimus given as a 60-minute intravenous (IV) infusion once weekly to pediatric subjects with advanced solid tumors. Part 1 is an ascending-dose study to evaluate the safety of IV temsirolimus given once weekly to subjects ages 1 to 21 years with advanced solid tumors disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available. (enrollment completed) Part 2 will be conducted in three groups of children with refractory or relapsed pediatric solid tumors. Subjects with the following tumor types will be enrolled: neuroblastoma, rhabdomyosarcoma, and high-grade gliomas. Subjects will receive IV temsirolimus once weekly until disease progression or unacceptable toxicity. (recruiting)
Interventions
DRUGTorisel
60-minute intravenous (IV) infusion once weekly to pediatric subjects with advanced solid tumors. Part 1 is an ascending-dose study to evaluate the safety of IV temsirolimus given once weekly to subjects ages 1 to 21 years with advanced solid tumors disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available. (enrollment completed) Part 2 will be conducted in three groups of children with refractory or relapsed pediatric solid tumors. Subjects with the following tumor types will be enrolled: neuroblastoma, rhabdomyosarcoma, and high-grade gliomas. Subjects will receive IV temsirolimus once weekly until disease progression or unacceptable toxicity.
Sponsors
Pfizer
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria: Part 1 only: \- Subjects with a histological diagnosis of advanced cancer (solid tumors or central nervous system \[CNS\] tumors) with disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available (histological confirmation waived for brain stem gliomas and optic pathway tumors) Part 2 only: * Subjects with histologically confirmed diagnosis of refractory or relapsed: Neuroblastoma, High-grade gliomas: glioblastoma multiforme, anaplastic astrocytomas, and other high-grade gliomas (histological confirmation waived for brain stem gliomas), Rhabdomyosarcoma. * Measurable disease (for subjects with neuroblastoma, evaluable disease as determined by a positive metaiodobenzylguanidine (MIBG) scan will also be permitted).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1 | Baseline up to End of Treatment (EOT) (within 30 days of last dose) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. |
| Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 1 | Baseline up to EOT (within 30 days of last dose) | TEAEs are events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs that occurred within 30 days of the last administration of study treatment can be attributed to the treatment period. |
| Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 1 | Baseline up to EOT (within 30 days of last dose) | TEAEs are events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs that occurred within 30 days of the last administration of study treatment can be attributed to the treatment period. National Cancer Institute (NCI)-graded Common Toxicity Criteria (CTC) provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided for each adverse event term. Grades range from 0 (none) to 5 (death). |
| Number of Participants Who Died: Part 1 | Baseline up to EOT (within 30 days of last dose) | Deaths were reported from baseline throughout the 30 day period after last study treatment. After the 30 day reporting period, only deaths believed related to study treatment were to be reported (as SAEs). |
| Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 1 | Baseline up to EOT (within 30 days of last dose) | SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability / incapacity or are a congenital anomaly or birth defect in the offspring of a study subject. Participants with documented study treatment toxicity were followed weekly until recovering. After the 30 day reporting period, only SAEs believed to be related to study treatment were to be reported. |
| Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 1 | Baseline up to EOT (within 30 days of last dose) | Temporary interruption of study treatment; may be followed by resumption of study treatment at current dose or dose modification as determined by the investigator and medical monitor. |
| Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 1 | Baseline up to EOT (within 30 days of last dose) | Dose reduction for individual participant allowed if a dose limiting toxicity (DLT) occurred; may continue treatment following reduction by 1 to 2 dose levels (determined by investigator and medical monitor). DLT= failure to recover to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of \>3 weeks) unless investigator and medical monitor agree participant should remain in the study. |
| Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1 | Baseline up to EOT (within 30 days of last dose) | Number of participants who met the criteria for PCI changes (based on baseline values before treatment); criteria defined as body temperature \>39 degrees Celsius (C), respiratory rate \>20 beats per minute (bpm), and systolic and diastolic blood pressure (BP) \>200/110 millimeters of mercury (mmHg). Participants may be reported in more than 1 category. |
| Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 1 | Baseline up to EOT (within 30 days of last dose) | Number of participants who met the PCI criteria (grades 1 through 5) for laboratory values (hematology and serum chemistry). NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided with grades ranging from 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), to 5 (death). Participants may be reported in more than 1 category. |
| Percentage of Participants With Objective Response (OR) at Week 12: Part 2 | Week 12 | Measured as Complete response (CR), Very good partial response (VGPR), or Partial response (PR) on at least 2 occasions greater than or equal to (\>=) 4 weeks apart within first 12 weeks. CR=disappearance of all primary and metastatic lesions; Homovanillic acid, Vanillymandelic acid (HVA/VMA) normal; bone marrow immunocytology negative. VGPR=disappearance of all metastatic lesions (residual areas of uptake on bone permitted); 90 to 99 percent (%) decrease in primary disease measurement; HVA/VMA normal or both decreased \>90%. PR=at least 50% decrease in primary and metastatic disease. Number of bone sites decreased by at least 50%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 | Baseline up to EOT (within 30 days of last dose) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. |
| Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 2 | Baseline up to EOT (within 30 days of last dose) | Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. |
| Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 2 | Baseline up to EOT (within 30 days of last dose) | Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided for each adverse event term. Grades range from 0 (none) to 5 (death). |
| Number of Participants Who Died: Part 2 | Baseline up to EOT (within 30 days of last dose) | Deaths were reported from baseline throughout the 30 day period after last study treatment. After the 30 day reporting period, only deaths believed related to study treatment were to be reported (as SAEs). |
| Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 2 | Baseline up to EOT (within 30 days of last dose) | An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Participants with documented study treatment toxicity were followed weekly until recovering. After the 30 day reporting period, only SAEs believed to be related to study treatment were to be reported. |
| Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 2 | Baseline up to EOT (within 30 days of last dose) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Temporary interruption of study treatment may be followed by resumption of study treatment at current dose or dose modification as determined by the investigator and medical monitor. |
| Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 2 | Baseline up to EOT (within 30 days of last dose) | Dose reduction for individual participant allowed if a DLT occurred; may continue treatment following reduction by 1 to 2 dose levels (determined by investigator and medical monitor). DLT= failure to recover to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of \>3 weeks) unless investigator and medical monitor agree participant should remain in the study. |
| Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 2 | Baseline up to EOT (within 30 days of last dose) | Number of participants who met the criteria for PCI changes (based on baseline values before treatment); criteria defined as body temperature \>39 degrees C, respiratory rate \>20 bpm, and systolic and diastolic BP \>200/110 mmHg. Participants may be reported in more than 1 category. |
| Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 2 | Baseline up to EOT (within 30 days of last dose) | Number of participants who met the PCI criteria (grades 1 through 5) for laboratory values (hematology and serum chemistry). NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided with grades ranging from 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), to 5 (death). Participants may be reported in more than 1 category. |
| Number of Participants Who Reached Maximum Tolerated Dose Due to Dose Limiting Toxicity: Part 1 | Baseline up to Month 6 | Maximum tolerated dose (MTD) defined as the dose level at which \>=2 of 3 participants or \>=2 of 6 participants if the dose level had been expanded, experienced a dose limiting toxicity (DLT) by day 21 after the first dose of study treatment. DLT defined as failure to recover to NCI-CTCAE version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of \> 3 weeks) unless the investigator and the medical monitor agree that the subject should remain in the study. |
| Average Plasma Concentration (Cavg): Part 2 | 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days) | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 2 | 0 (pre-dose),1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days) | — |
| Plasma Decay Half-Life (t1/2): Part 2 | 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 2 | 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days) | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) |
| Area Under the Concentration-time Curve at Steady State (AUCss): Part 2 | 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days) | AUCss is a measure of the serum concentration of the drug at steady state. It is used to characterize drug absorption. |
| Clearance (CL): Part 2 | 0 (pre-dose),1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days) | CL is a quantitative measure of the rate at which a drug substance is removed from the body. |
| Concentration in Plasma (Cp) and Concentration in Plasma at Time Zero (Cp Time 0): Part 1 and Part 2 | Part 1: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2; Part2: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days) | Pharmacokinetic parameters determined in whole blood; derived from the concentration-versus-time profiles using noncompartmental analysis method. Measured as nanograms per milliliter (ng/mL). |
| Number of Participants for Change From Baseline in the Phosphorylation of Mammalian Target of Rapamycin (mTOR) Pathway Proteins: Part 1 and Part 2 | Part 1:Baseline,1,2,6,24,168 hrs post-dose of Cycle 1;additional 0 (Pre-dose),24,72,96 hrs, Day 16 to 21 of cycle 2, EOT(within 30 days of last dose); Part 2:Baseline,Day16 to 21 in Cycle 2, at time of disease progression, EOT(within 30 days of last dose) | Optional bone marrow sampling for pharmacodynamic analysis of effects of study treatment. Data may not be collected for a majority of patients and was not to be summarized if collection was sparse. |
| Maximum Observed Plasma Concentration (Cmax): Part 2 | 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days) | — |
| Maximum Observed Plasma Concentration (Cmax): Part 1 | 0 (pre-dose), 1, 2, 6, 24, and 168 hours (hrs) post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days) | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 1 | 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days) | — |
| Plasma Decay Half-Life (t1/2): Part 1 | 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 1 | 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days) | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t). |
| Area Under the Concentration-Time Curve (AUC): Part 1 | 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days) | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. |
| Clearance (CL): Part 1 | 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days) | CL is a quantitative measure of the rate at which a drug substance is removed from the body. |
| Volume of Distribution at Steady State (Vss): Part 1 | 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days) | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. |
| Percentage of Participants With Best Overall Response: Part 1 | Baseline until disease progression or recurrence (actual greatest response day is up to Day 49) | Best overall response is the best response recorded from baseline until disease progression or recurrence. Measured as CR, PR, SD, PD, or Unknown. CR=disappearance of all primary and metastatic lesions. PR=at least a 50% decrease in primary disease measurement. SD=no new lesions; decrease of \<50% in all lesions with no lesion increasing \>25%. PD=any new lesion; at least a 25% increase in any disease measurement (reference smallest disease measurement recorded since start of treatment); or appearance of 1 or more new lesions. Tumor response considered Unknown if assessment prior to Day 37. |
| Percentage of Participants Exhibiting Freedom From Progression at Week 12: Part 2 | Week 12 | Freedom from progression measured as Stable Disease (SD) or better and no Progressive Disease (PD); (CR+VGPR+Mixed Response \[MR\]+PR+SD). CR=disappearance of all primary and metastatic lesions. VGPR=disappearance of all metastatic lesions. MR=no new lesions; at least 50% decrease in any 1 disease measurement with \<50% decrease in any other disease measurement or an increase of \<25% in any lesion). SD=no new lesions; decrease of \<50% in all lesions with no lesion increasing \>25%. PD=at least a 25% increase in any disease measurement; or the appearance of 1 or more new lesions. |
Countries
Canada, France, Germany, Mexico, Poland, Russia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1 Participants received temsirolimus intravenously once weekly over 60 minutes infusion in dose escalation schemes of 10 mg/m\^2, 25 mg/m\^2, 75 mg/m\^2 and 150 mg/m\^2. | 19 |
| Part 2 Participants with high-grade glioma, neuroblastoma and rhabdomyosarcoma were administered temsirolimus 75 mg/m\^2 intravenously once weekly over 60 minutes infusion. | 52 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Part 1 | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Part 1 | Disease progression | 3 | 4 | 1 | 3 | 0 | 0 | 0 |
| Part 1 | Entered follow-up phase | 1 | 1 | 0 | 1 | 0 | 0 | 0 |
| Part 1 | Symptomatic deterioration | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Part 1 | Withdrawal by Subject | 0 | 0 | 1 | 2 | 0 | 0 | 0 |
| Part 2 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 2 | 1 |
| Part 2 | Death | 0 | 0 | 0 | 0 | 3 | 0 | 1 |
| Part 2 | Disease progression | 0 | 0 | 0 | 0 | 8 | 14 | 13 |
| Part 2 | Other | 0 | 0 | 0 | 0 | 1 | 1 | 1 |
| Part 2 | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part 2 | Symptomatic deterioration | 0 | 0 | 0 | 0 | 3 | 0 | 0 |
| Part 2 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1 | Part 2 | Total |
|---|---|---|---|
| Age, Customized >=16 to less than 18 years | 2 participants | 3 participants | 5 participants |
| Age, Customized >=18 to less than or equal to 21 years | 5 participants | 7 participants | 12 participants |
| Age, Customized Greater than or equal to(>=)1 to less than16 years | 12 participants | 42 participants | 54 participants |
| Sex: Female, Male Female | 8 Participants | 17 Participants | 25 Participants |
| Sex: Female, Male Male | 11 Participants | 35 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 5 / 5 | 3 / 3 | 7 / 7 | 17 / 17 | 19 / 19 | 15 / 16 |
| serious Total, serious adverse events | 2 / 4 | 2 / 5 | 2 / 3 | 3 / 7 | 10 / 17 | 6 / 19 | 6 / 16 |
Outcome results
Primary
Number of Participants Who Died: Part 1
Deaths were reported from baseline throughout the 30 day period after last study treatment. After the 30 day reporting period, only deaths believed related to study treatment were to be reported (as SAEs).
Time frame: Baseline up to EOT (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants Who Died: Part 1 | Died=Yes | 3 participants |
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants Who Died: Part 1 | Died within 30 days of last dose | 2 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants Who Died: Part 1 | Died=Yes | 1 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants Who Died: Part 1 | Died within 30 days of last dose | 0 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants Who Died: Part 1 | Died=Yes | 0 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants Who Died: Part 1 | Died within 30 days of last dose | 0 participants |
| Temsirolimus 150 mg/m^2: Part 1 | Number of Participants Who Died: Part 1 | Died within 30 days of last dose | 0 participants |
| Temsirolimus 150 mg/m^2: Part 1 | Number of Participants Who Died: Part 1 | Died=Yes | 0 participants |
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: Baseline up to End of Treatment (EOT) (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1 | AEs | 4 participants |
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1 | SAEs | 2 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1 | SAEs | 2 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1 | AEs | 5 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1 | AEs | 3 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1 | SAEs | 2 participants |
| Temsirolimus 150 mg/m^2: Part 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1 | AEs | 7 participants |
| Temsirolimus 150 mg/m^2: Part 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1 | SAEs | 3 participants |
Primary
Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 1
Dose reduction for individual participant allowed if a dose limiting toxicity (DLT) occurred; may continue treatment following reduction by 1 to 2 dose levels (determined by investigator and medical monitor). DLT= failure to recover to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of \>3 weeks) unless investigator and medical monitor agree participant should remain in the study.
Time frame: Baseline up to EOT (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 1 | 0 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 1 | 0 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 1 | 0 participants |
| Temsirolimus 150 mg/m^2: Part 1 | Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 1 | 1 participants |
Primary
Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 1
Temporary interruption of study treatment; may be followed by resumption of study treatment at current dose or dose modification as determined by the investigator and medical monitor.
Time frame: Baseline up to EOT (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 1 | 0 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 1 | 2 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 1 | 1 participants |
| Temsirolimus 150 mg/m^2: Part 1 | Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 1 | 2 participants |
Primary
Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 1
TEAEs are events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs that occurred within 30 days of the last administration of study treatment can be attributed to the treatment period. National Cancer Institute (NCI)-graded Common Toxicity Criteria (CTC) provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided for each adverse event term. Grades range from 0 (none) to 5 (death).
Time frame: Baseline up to EOT (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 1 | 1 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 1 | 2 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 1 | 2 participants |
| Temsirolimus 150 mg/m^2: Part 1 | Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 1 | 4 participants |
Primary
Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 1
SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability / incapacity or are a congenital anomaly or birth defect in the offspring of a study subject. Participants with documented study treatment toxicity were followed weekly until recovering. After the 30 day reporting period, only SAEs believed to be related to study treatment were to be reported.
Time frame: Baseline up to EOT (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 1 | 0 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 1 | 0 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 1 | 0 participants |
| Temsirolimus 150 mg/m^2: Part 1 | Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 1 | 1 participants |
Primary
Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 1
TEAEs are events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs that occurred within 30 days of the last administration of study treatment can be attributed to the treatment period.
Time frame: Baseline up to EOT (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 1 | 4 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 1 | 5 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 1 | 3 participants |
| Temsirolimus 150 mg/m^2: Part 1 | Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 1 | 7 participants |
Primary
Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1
Number of participants who met the criteria for PCI changes (based on baseline values before treatment); criteria defined as body temperature \>39 degrees Celsius (C), respiratory rate \>20 beats per minute (bpm), and systolic and diastolic blood pressure (BP) \>200/110 millimeters of mercury (mmHg). Participants may be reported in more than 1 category.
Time frame: Baseline up to EOT (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1 | Respiratory rate >20 bpm | 4 participants |
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1 | Systolic/Diastolic BP >200/110 mmHg | 0 participants |
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1 | Temperature >39 degrees C | 1 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1 | Systolic/Diastolic BP >200/110 mmHg | 0 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1 | Temperature >39 degrees C | 2 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1 | Respiratory rate >20 bpm | 5 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1 | Respiratory rate >20 bpm | 3 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1 | Temperature >39 degrees C | 1 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1 | Systolic/Diastolic BP >200/110 mmHg | 0 participants |
| Temsirolimus 150 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1 | Temperature >39 degrees C | 3 participants |
| Temsirolimus 150 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1 | Systolic/Diastolic BP >200/110 mmHg | 0 participants |
| Temsirolimus 150 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1 | Respiratory rate >20 bpm | 7 participants |
Primary
Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 1
Number of participants who met the PCI criteria (grades 1 through 5) for laboratory values (hematology and serum chemistry). NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided with grades ranging from 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), to 5 (death). Participants may be reported in more than 1 category.
Time frame: Baseline up to EOT (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 1 | 4 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 1 | 5 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 1 | 3 participants |
| Temsirolimus 150 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 1 | 7 participants |
Primary
Percentage of Participants With Objective Response (OR) at Week 12: Part 2
Measured as Complete response (CR), Very good partial response (VGPR), or Partial response (PR) on at least 2 occasions greater than or equal to (\>=) 4 weeks apart within first 12 weeks. CR=disappearance of all primary and metastatic lesions; Homovanillic acid, Vanillymandelic acid (HVA/VMA) normal; bone marrow immunocytology negative. VGPR=disappearance of all metastatic lesions (residual areas of uptake on bone permitted); 90 to 99 percent (%) decrease in primary disease measurement; HVA/VMA normal or both decreased \>90%. PR=at least 50% decrease in primary and metastatic disease. Number of bone sites decreased by at least 50%.
Time frame: Week 12
Population: Efficacy evaluable population included all participants who received at least 3 doses of study treatment. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Percentage of Participants With Objective Response (OR) at Week 12: Part 2 | 0.00 percentage of participants |
| Temsirolimus 25 mg/m^2: Part 1 | Percentage of Participants With Objective Response (OR) at Week 12: Part 2 | 6.67 percentage of participants |
| Temsirolimus 75 mg/m^2: Part 1 | Percentage of Participants With Objective Response (OR) at Week 12: Part 2 | 0.00 percentage of participants |
Secondary
Area Under the Concentration-time Curve at Steady State (AUCss): Part 2
AUCss is a measure of the serum concentration of the drug at steady state. It is used to characterize drug absorption.
Time frame: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Area Under the Concentration-time Curve at Steady State (AUCss): Part 2 | 13900 hr*ng/mL | Standard Deviation 24100 |
Secondary
Area Under the Concentration-Time Curve (AUC): Part 1
AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Time frame: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for each group respectively. Here, 'n' signifies those participants who were evaluable for particular cycle for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Area Under the Concentration-Time Curve (AUC): Part 1 | Cycle 1 (n = 4, 4, 1, 4) | 2000 hr*ng/mL | Standard Deviation 959 |
| Temsirolimus 10 mg/m^2: Part 1 | Area Under the Concentration-Time Curve (AUC): Part 1 | Cycle 2 (n = 4, 3, 3, 5) | 1600 hr*ng/mL | Standard Deviation 540 |
| Temsirolimus 25 mg/m^2: Part 1 | Area Under the Concentration-Time Curve (AUC): Part 1 | Cycle 2 (n = 4, 3, 3, 5) | 2580 hr*ng/mL | Standard Deviation 768 |
| Temsirolimus 25 mg/m^2: Part 1 | Area Under the Concentration-Time Curve (AUC): Part 1 | Cycle 1 (n = 4, 4, 1, 4) | 4640 hr*ng/mL | Standard Deviation 3430 |
| Temsirolimus 75 mg/m^2: Part 1 | Area Under the Concentration-Time Curve (AUC): Part 1 | Cycle 1 (n = 4, 4, 1, 4) | 2810 hr*ng/mL | — |
| Temsirolimus 75 mg/m^2: Part 1 | Area Under the Concentration-Time Curve (AUC): Part 1 | Cycle 2 (n = 4, 3, 3, 5) | 3500 hr*ng/mL | Standard Deviation 1140 |
| Temsirolimus 150 mg/m^2: Part 1 | Area Under the Concentration-Time Curve (AUC): Part 1 | Cycle 1 (n = 4, 4, 1, 4) | 13000 hr*ng/mL | Standard Deviation 17000 |
| Temsirolimus 150 mg/m^2: Part 1 | Area Under the Concentration-Time Curve (AUC): Part 1 | Cycle 2 (n = 4, 3, 3, 5) | 4960 hr*ng/mL | Standard Deviation 2000 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 1
AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t).
Time frame: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were evaluable for particular cycle for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 1 | Cycle 1 (n = 4, 5, 3, 7) | 1670 hr*ng/mL | Standard Deviation 730 |
| Temsirolimus 10 mg/m^2: Part 1 | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 1 | Cycle 2 (n = 4, 4, 3, 5) | 1520 hr*ng/mL | Standard Deviation 583 |
| Temsirolimus 25 mg/m^2: Part 1 | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 1 | Cycle 2 (n = 4, 4, 3, 5) | 1930 hr*ng/mL | Standard Deviation 1090 |
| Temsirolimus 25 mg/m^2: Part 1 | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 1 | Cycle 1 (n = 4, 5, 3, 7) | 3890 hr*ng/mL | Standard Deviation 3190 |
| Temsirolimus 75 mg/m^2: Part 1 | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 1 | Cycle 1 (n = 4, 5, 3, 7) | 3750 hr*ng/mL | Standard Deviation 2420 |
| Temsirolimus 75 mg/m^2: Part 1 | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 1 | Cycle 2 (n = 4, 4, 3, 5) | 3420 hr*ng/mL | Standard Deviation 1230 |
| Temsirolimus 150 mg/m^2: Part 1 | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 1 | Cycle 1 (n = 4, 5, 3, 7) | 9680 hr*ng/mL | Standard Deviation 12800 |
| Temsirolimus 150 mg/m^2: Part 1 | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 1 | Cycle 2 (n = 4, 4, 3, 5) | 4850 hr*ng/mL | Standard Deviation 1810 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 2
AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)
Time frame: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 2 | 13100 hr*ng/mL | Standard Deviation 22700 |
Secondary
Average Plasma Concentration (Cavg): Part 2
Time frame: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Average Plasma Concentration (Cavg): Part 2 | 82.8 ng/mL | Standard Deviation 143 |
Secondary
Clearance (CL): Part 1
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for each group respectively. Here, 'n' signifies those participants who were evaluable for particular cycle for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Clearance (CL): Part 1 | Cycle 2 (n = 4, 3, 3, 5) | 8.99 Liter/hr | Standard Deviation 5.27 |
| Temsirolimus 10 mg/m^2: Part 1 | Clearance (CL): Part 1 | Cycle 1 (n = 4, 4, 1, 4) | 7.02 Liter/hr | Standard Deviation 3.68 |
| Temsirolimus 25 mg/m^2: Part 1 | Clearance (CL): Part 1 | Cycle 1 (n = 4, 4, 1, 4) | 10.4 Liter/hr | Standard Deviation 6.45 |
| Temsirolimus 25 mg/m^2: Part 1 | Clearance (CL): Part 1 | Cycle 2 (n = 4, 3, 3, 5) | 13.8 Liter/hr | Standard Deviation 9.06 |
| Temsirolimus 75 mg/m^2: Part 1 | Clearance (CL): Part 1 | Cycle 1 (n = 4, 4, 1, 4) | 38.1 Liter/hr | — |
| Temsirolimus 75 mg/m^2: Part 1 | Clearance (CL): Part 1 | Cycle 2 (n = 4, 3, 3, 5) | 30.6 Liter/hr | Standard Deviation 15.5 |
| Temsirolimus 150 mg/m^2: Part 1 | Clearance (CL): Part 1 | Cycle 1 (n = 4, 4, 1, 4) | 47.9 Liter/hr | Standard Deviation 45.8 |
| Temsirolimus 150 mg/m^2: Part 1 | Clearance (CL): Part 1 | Cycle 2 (n = 4, 3, 3, 5) | 39 Liter/hr | Standard Deviation 24.4 |
Secondary
Clearance (CL): Part 2
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: 0 (pre-dose),1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Clearance (CL): Part 2 | 14.3 L/hr | Standard Deviation 14 |
Secondary
Concentration in Plasma (Cp) and Concentration in Plasma at Time Zero (Cp Time 0): Part 1 and Part 2
Pharmacokinetic parameters determined in whole blood; derived from the concentration-versus-time profiles using noncompartmental analysis method. Measured as nanograms per milliliter (ng/mL).
Time frame: Part 1: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2; Part2: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Population: Data was not analyzed.
Secondary
Maximum Observed Plasma Concentration (Cmax): Part 1
Time frame: 0 (pre-dose), 1, 2, 6, 24, and 168 hours (hrs) post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were evaluable for particular cycle for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Maximum Observed Plasma Concentration (Cmax): Part 1 | Cycle 2 (n = 4, 4, 3, 5) | 252 nanogram per milliliter (ng/mL) | Standard Deviation 98.3 |
| Temsirolimus 10 mg/m^2: Part 1 | Maximum Observed Plasma Concentration (Cmax): Part 1 | Cycle 1 (n = 4, 5, 3, 7) | 307 nanogram per milliliter (ng/mL) | Standard Deviation 91.3 |
| Temsirolimus 25 mg/m^2: Part 1 | Maximum Observed Plasma Concentration (Cmax): Part 1 | Cycle 2 (n = 4, 4, 3, 5) | 403 nanogram per milliliter (ng/mL) | Standard Deviation 128 |
| Temsirolimus 25 mg/m^2: Part 1 | Maximum Observed Plasma Concentration (Cmax): Part 1 | Cycle 1 (n = 4, 5, 3, 7) | 487 nanogram per milliliter (ng/mL) | Standard Deviation 141 |
| Temsirolimus 75 mg/m^2: Part 1 | Maximum Observed Plasma Concentration (Cmax): Part 1 | Cycle 1 (n = 4, 5, 3, 7) | 480 nanogram per milliliter (ng/mL) | Standard Deviation 135 |
| Temsirolimus 75 mg/m^2: Part 1 | Maximum Observed Plasma Concentration (Cmax): Part 1 | Cycle 2 (n = 4, 4, 3, 5) | 807 nanogram per milliliter (ng/mL) | Standard Deviation 279 |
| Temsirolimus 150 mg/m^2: Part 1 | Maximum Observed Plasma Concentration (Cmax): Part 1 | Cycle 2 (n = 4, 4, 3, 5) | 2570 nanogram per milliliter (ng/mL) | Standard Deviation 1110 |
| Temsirolimus 150 mg/m^2: Part 1 | Maximum Observed Plasma Concentration (Cmax): Part 1 | Cycle 1 (n = 4, 5, 3, 7) | 9230 nanogram per milliliter (ng/mL) | Standard Deviation 18200 |
Secondary
Maximum Observed Plasma Concentration (Cmax): Part 2
Time frame: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Maximum Observed Plasma Concentration (Cmax): Part 2 | 6280 ng/mL | Standard Deviation 21000 |
Secondary
Number of Participants for Change From Baseline in the Phosphorylation of Mammalian Target of Rapamycin (mTOR) Pathway Proteins: Part 1 and Part 2
Optional bone marrow sampling for pharmacodynamic analysis of effects of study treatment. Data may not be collected for a majority of patients and was not to be summarized if collection was sparse.
Time frame: Part 1:Baseline,1,2,6,24,168 hrs post-dose of Cycle 1;additional 0 (Pre-dose),24,72,96 hrs, Day 16 to 21 of cycle 2, EOT(within 30 days of last dose); Part 2:Baseline,Day16 to 21 in Cycle 2, at time of disease progression, EOT(within 30 days of last dose)
Population: Data was not analyzed.
Secondary
Number of Participants Who Died: Part 2
Deaths were reported from baseline throughout the 30 day period after last study treatment. After the 30 day reporting period, only deaths believed related to study treatment were to be reported (as SAEs).
Time frame: Baseline up to EOT (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants Who Died: Part 2 | Died=Yes | 5 participants |
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants Who Died: Part 2 | Died within 30 days of last dose | 3 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants Who Died: Part 2 | Died=Yes | 2 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants Who Died: Part 2 | Died within 30 days of last dose | 0 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants Who Died: Part 2 | Died=Yes | 4 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants Who Died: Part 2 | Died within 30 days of last dose | 3 participants |
Secondary
Number of Participants Who Reached Maximum Tolerated Dose Due to Dose Limiting Toxicity: Part 1
Maximum tolerated dose (MTD) defined as the dose level at which \>=2 of 3 participants or \>=2 of 6 participants if the dose level had been expanded, experienced a dose limiting toxicity (DLT) by day 21 after the first dose of study treatment. DLT defined as failure to recover to NCI-CTCAE version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of \> 3 weeks) unless the investigator and the medical monitor agree that the subject should remain in the study.
Time frame: Baseline up to Month 6
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants Who Reached Maximum Tolerated Dose Due to Dose Limiting Toxicity: Part 1 | 0 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants Who Reached Maximum Tolerated Dose Due to Dose Limiting Toxicity: Part 1 | 0 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants Who Reached Maximum Tolerated Dose Due to Dose Limiting Toxicity: Part 1 | 0 participants |
| Temsirolimus 150 mg/m^2: Part 1 | Number of Participants Who Reached Maximum Tolerated Dose Due to Dose Limiting Toxicity: Part 1 | 2 participants |
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: Baseline up to EOT (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 | AEs | 17 participants |
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 | SAEs | 10 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 | AEs | 19 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 | SAEs | 6 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 | AEs | 16 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 | SAEs | 6 participants |
Secondary
Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 2
Dose reduction for individual participant allowed if a DLT occurred; may continue treatment following reduction by 1 to 2 dose levels (determined by investigator and medical monitor). DLT= failure to recover to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of \>3 weeks) unless investigator and medical monitor agree participant should remain in the study.
Time frame: Baseline up to EOT (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 2 | 5 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 2 | 10 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 2 | 6 participants |
Secondary
Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 2
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Temporary interruption of study treatment may be followed by resumption of study treatment at current dose or dose modification as determined by the investigator and medical monitor.
Time frame: Baseline up to EOT (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 2 | 9 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 2 | 12 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 2 | 6 participants |
Secondary
Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 2
Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided for each adverse event term. Grades range from 0 (none) to 5 (death).
Time frame: Baseline up to EOT (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 2 | 5 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 2 | 11 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 2 | 6 participants |
Secondary
Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 2
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Participants with documented study treatment toxicity were followed weekly until recovering. After the 30 day reporting period, only SAEs believed to be related to study treatment were to be reported.
Time frame: Baseline up to EOT (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 2 | 2 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 2 | 3 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 2 | 3 participants |
Secondary
Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 2
Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Baseline up to EOT (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 2 | 17 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 2 | 18 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 2 | 13 participants |
Secondary
Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 2
Number of participants who met the criteria for PCI changes (based on baseline values before treatment); criteria defined as body temperature \>39 degrees C, respiratory rate \>20 bpm, and systolic and diastolic BP \>200/110 mmHg. Participants may be reported in more than 1 category.
Time frame: Baseline up to EOT (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 2 | Systolic/Diastolic BP >200/110 mmHg | 1 participants |
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 2 | Respiratory rate >20 bpm | 16 participants |
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 2 | Temperature >39 degrees C | 0 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 2 | Respiratory rate >20 bpm | 18 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 2 | Temperature >39 degrees C | 0 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 2 | Systolic/Diastolic BP >200/110 mmHg | 0 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 2 | Temperature >39 degrees C | 0 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 2 | Systolic/Diastolic BP >200/110 mmHg | 0 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 2 | Respiratory rate >20 bpm | 14 participants |
Secondary
Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 2
Number of participants who met the PCI criteria (grades 1 through 5) for laboratory values (hematology and serum chemistry). NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided with grades ranging from 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), to 5 (death). Participants may be reported in more than 1 category.
Time frame: Baseline up to EOT (within 30 days of last dose)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 2 | 17 participants |
| Temsirolimus 25 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 2 | 19 participants |
| Temsirolimus 75 mg/m^2: Part 1 | Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 2 | 15 participants |
Secondary
Percentage of Participants Exhibiting Freedom From Progression at Week 12: Part 2
Freedom from progression measured as Stable Disease (SD) or better and no Progressive Disease (PD); (CR+VGPR+Mixed Response \[MR\]+PR+SD). CR=disappearance of all primary and metastatic lesions. VGPR=disappearance of all metastatic lesions. MR=no new lesions; at least 50% decrease in any 1 disease measurement with \<50% decrease in any other disease measurement or an increase of \<25% in any lesion). SD=no new lesions; decrease of \<50% in all lesions with no lesion increasing \>25%. PD=at least a 25% increase in any disease measurement; or the appearance of 1 or more new lesions.
Time frame: Week 12
Population: Efficacy evaluable population included all participants who received at least 3 doses of study treatment. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Percentage of Participants Exhibiting Freedom From Progression at Week 12: Part 2 | 46.67 percentage of participants |
| Temsirolimus 25 mg/m^2: Part 1 | Percentage of Participants Exhibiting Freedom From Progression at Week 12: Part 2 | 40.00 percentage of participants |
| Temsirolimus 75 mg/m^2: Part 1 | Percentage of Participants Exhibiting Freedom From Progression at Week 12: Part 2 | 8.33 percentage of participants |
Secondary
Percentage of Participants With Best Overall Response: Part 1
Best overall response is the best response recorded from baseline until disease progression or recurrence. Measured as CR, PR, SD, PD, or Unknown. CR=disappearance of all primary and metastatic lesions. PR=at least a 50% decrease in primary disease measurement. SD=no new lesions; decrease of \<50% in all lesions with no lesion increasing \>25%. PD=any new lesion; at least a 25% increase in any disease measurement (reference smallest disease measurement recorded since start of treatment); or appearance of 1 or more new lesions. Tumor response considered Unknown if assessment prior to Day 37.
Time frame: Baseline until disease progression or recurrence (actual greatest response day is up to Day 49)
Population: Efficacy evaluable population included all participants who received at least 3 doses of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Progressive disease | 3 percentage of participants |
| Temsirolimus 10 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Partial response | 0 percentage of participants |
| Temsirolimus 10 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Unknown response | 0 percentage of participants |
| Temsirolimus 10 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Stable disease | 0 percentage of participants |
| Temsirolimus 10 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Complete response | 1 percentage of participants |
| Temsirolimus 25 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Stable disease | 2 percentage of participants |
| Temsirolimus 25 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Progressive disease | 2 percentage of participants |
| Temsirolimus 25 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Unknown response | 0 percentage of participants |
| Temsirolimus 25 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Partial response | 0 percentage of participants |
| Temsirolimus 25 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Complete response | 0 percentage of participants |
| Temsirolimus 75 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Stable disease | 3 percentage of participants |
| Temsirolimus 75 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Complete response | 0 percentage of participants |
| Temsirolimus 75 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Partial response | 0 percentage of participants |
| Temsirolimus 75 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Progressive disease | 0 percentage of participants |
| Temsirolimus 75 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Unknown response | 0 percentage of participants |
| Temsirolimus 150 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Progressive disease | 3 percentage of participants |
| Temsirolimus 150 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Partial response | 0 percentage of participants |
| Temsirolimus 150 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Complete response | 0 percentage of participants |
| Temsirolimus 150 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Stable disease | 2 percentage of participants |
| Temsirolimus 150 mg/m^2: Part 1 | Percentage of Participants With Best Overall Response: Part 1 | Unknown response | 2 percentage of participants |
Secondary
Plasma Decay Half-Life (t1/2): Part 1
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for each group respectively. Here, 'n' signifies those participants who were evaluable for particular cycle for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Plasma Decay Half-Life (t1/2): Part 1 | Cycle 1 (n = 4, 4, 1, 4) | 10.6 hr | Standard Deviation 0.556 |
| Temsirolimus 10 mg/m^2: Part 1 | Plasma Decay Half-Life (t1/2): Part 1 | Cycle 2 (n = 4, 3, 3, 5) | 14.4 hr | Standard Deviation 4.42 |
| Temsirolimus 25 mg/m^2: Part 1 | Plasma Decay Half-Life (t1/2): Part 1 | Cycle 2 (n = 4, 3, 3, 5) | 14.3 hr | Standard Deviation 10.4 |
| Temsirolimus 25 mg/m^2: Part 1 | Plasma Decay Half-Life (t1/2): Part 1 | Cycle 1 (n = 4, 4, 1, 4) | 16.4 hr | Standard Deviation 6.9 |
| Temsirolimus 75 mg/m^2: Part 1 | Plasma Decay Half-Life (t1/2): Part 1 | Cycle 1 (n = 4, 4, 1, 4) | 24 hr | — |
| Temsirolimus 75 mg/m^2: Part 1 | Plasma Decay Half-Life (t1/2): Part 1 | Cycle 2 (n = 4, 3, 3, 5) | 25.4 hr | Standard Deviation 1.83 |
| Temsirolimus 150 mg/m^2: Part 1 | Plasma Decay Half-Life (t1/2): Part 1 | Cycle 1 (n = 4, 4, 1, 4) | 19.3 hr | Standard Deviation 10.5 |
| Temsirolimus 150 mg/m^2: Part 1 | Plasma Decay Half-Life (t1/2): Part 1 | Cycle 2 (n = 4, 3, 3, 5) | 24.2 hr | Standard Deviation 7.58 |
Secondary
Plasma Decay Half-Life (t1/2): Part 2
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Plasma Decay Half-Life (t1/2): Part 2 | 30.65 hr | Standard Deviation 13.63 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 1
Time frame: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were evaluable for particular cycle for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 1 | Cycle 1 (n = 4, 5, 3, 7) | 1 hr | Standard Deviation 0.143 |
| Temsirolimus 10 mg/m^2: Part 1 | Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 1 | Cycle 2 (n = 4, 4, 3, 5) | 1.1 hr | Standard Deviation 0.236 |
| Temsirolimus 25 mg/m^2: Part 1 | Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 1 | Cycle 2 (n = 4, 4, 3, 5) | 1.7 hr | Standard Deviation 0.983 |
| Temsirolimus 25 mg/m^2: Part 1 | Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 1 | Cycle 1 (n = 4, 5, 3, 7) | 1.1 hr | Standard Deviation 0.074 |
| Temsirolimus 75 mg/m^2: Part 1 | Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 1 | Cycle 1 (n = 4, 5, 3, 7) | 1.3 hr | Standard Deviation 0.231 |
| Temsirolimus 75 mg/m^2: Part 1 | Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 1 | Cycle 2 (n = 4, 4, 3, 5) | 1.2 hr | Standard Deviation 0.202 |
| Temsirolimus 150 mg/m^2: Part 1 | Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 1 | Cycle 1 (n = 4, 5, 3, 7) | 1.1 hr | Standard Deviation 0.218 |
| Temsirolimus 150 mg/m^2: Part 1 | Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 1 | Cycle 2 (n = 4, 4, 3, 5) | 1.2 hr | Standard Deviation 0.212 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 2
Time frame: 0 (pre-dose),1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 2 | 1.00 hr |
Secondary
Volume of Distribution at Steady State (Vss): Part 1
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Time frame: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for each group respectively. Here, 'n' signifies those participants who were evaluable for particular cycle for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Temsirolimus 10 mg/m^2: Part 1 | Volume of Distribution at Steady State (Vss): Part 1 | Cycle 1 (n = 4, 4, 1, 4) | 85.2 Liter | Standard Deviation 35 |
| Temsirolimus 10 mg/m^2: Part 1 | Volume of Distribution at Steady State (Vss): Part 1 | Cycle 2 (n = 4, 3, 3, 5) | 250 Liter | Standard Deviation 290 |
| Temsirolimus 25 mg/m^2: Part 1 | Volume of Distribution at Steady State (Vss): Part 1 | Cycle 2 (n = 4, 3, 3, 5) | 201 Liter | Standard Deviation 132 |
| Temsirolimus 25 mg/m^2: Part 1 | Volume of Distribution at Steady State (Vss): Part 1 | Cycle 1 (n = 4, 4, 1, 4) | 189 Liter | Standard Deviation 44.2 |
| Temsirolimus 75 mg/m^2: Part 1 | Volume of Distribution at Steady State (Vss): Part 1 | Cycle 1 (n = 4, 4, 1, 4) | 783 Liter | — |
| Temsirolimus 75 mg/m^2: Part 1 | Volume of Distribution at Steady State (Vss): Part 1 | Cycle 2 (n = 4, 3, 3, 5) | 601 Liter | Standard Deviation 347 |
| Temsirolimus 150 mg/m^2: Part 1 | Volume of Distribution at Steady State (Vss): Part 1 | Cycle 1 (n = 4, 4, 1, 4) | 512 Liter | Standard Deviation 689 |
| Temsirolimus 150 mg/m^2: Part 1 | Volume of Distribution at Steady State (Vss): Part 1 | Cycle 2 (n = 4, 3, 3, 5) | 353 Liter | Standard Deviation 130 |