Prostate Cancer
Conditions
Brief summary
Primary Objectives: * To determine the maximum tolerated dose, and dose limiting toxicities of cabazitaxel administered as a 1-hour infusion every 3 weeks in combination with oral daily abiraterone acetate and prednisone in participants with metastatic Castrate-resistant prostate cancer (CRPC) * To estimate the anti-tumor activity of cabazitaxel in combination with abiraterone acetate and prednisone in terms of prostate-specific antigen (PSA) response rate. Secondary Objectives: * To characterize the safety profile of the combination * To evaluate the pharmacokinetic profile of cabazitaxel and abiraterone in the proposed combination and dosing schedule * To assess preliminary antitumor activity of the combination in terms of progression-free survival, PSA progression free survival and objective response rate, and overall survival
Detailed description
The study duration was to include a period for inclusion of up to 3 weeks and a 3-week treatment cycle(s). The participants might continue treatment until disease progression, unacceptable toxicity or willingness to stop followed by a minimum of 30-day follow-up
Interventions
Pharmaceutical form:solution Route of administration: injection
DRUGAbiraterone acetate
Pharmaceutical form:tablets Route of administration: oral
DRUGPrednisone 5 mg
Route of administration: oral
Sponsors
Sanofi
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Diagnosis of prostate adenocarcinoma proven histologically or cytologically, resistant to hormone therapy and previously treated with a docetaxel-containing regimen. In Phase 2 part, participants should have been treated with abiraterone acetate for at least 3 months and should continue treatment with abiraterone acetate before study entry * Presence of metastatic prostate cancer. * Participant must had progressive disease documented by rising PSA defined as 2 sequential increases above a previous lowest reference value (each PSA value must be obtained at least 1 week apart. A PSA value of at least 6 ng/mL was required at study entry). In Phase 1 part, in addition to rising PSA, progressive disease must be documented by: 1. Increase in non-measureable or measurable disease, and/or 2. Appearance of new lesions, including those on bone scan (≥2 new lesions on 2 consecutive bone scans if progressive disease diagnosed on bone scan only) consistent with progressive prostate cancer * Effective castration (serum testosterone levels ≤0.50 ng/mL) by orchiectomy and/or luteinizing hormone-releasing hormone agonists /antagonist. 1. If the participant had been treated with luteinizing hormone-releasing hormone agonists/antagonist (i.e., without orchiectomy), then this therapy had been initiated at least 4 weeks prior to cycle 1 day 1 and should be continued throughout the study. 2. Prior anti-androgen therapy should be stopped before enrollment * Eastern Cooperative Oncology Group performance status: 0 - 1.
Exclusion criteria
Previous treatment with mitoxantrone or cabazitaxel. * Prior bone-seeking radio-isotope therapy (participants treated with Radium223 were not excluded from the study). Radiotherapy to ≥30% of bone marrow. * Adverse events from any prior anticancer therapy of grade \>1 at the time of enrollment. Prior surgery, radiation, chemotherapy, or other anti-cancer therapy within 4 weeks prior to enrollment in the study (except luteinizing hormone-releasing hormone agonist /antagonist and abiraterone acetate in the Phase 2 part of the study); small field single fraction palliative radiation within 1 week. * Prior malignancy. Curatively treated basal cell or squamous cell skin or superficial (pTis, pTa, and pT1) bladder cancer were allowed, as well as any other cancer for which chemotherapy had been completed ≥ 3 years ago and from which the participant had been disease-free for ≥ 3 years. * Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to enrollment. * Known brain or leptomeningeal metastases. * Any severe acute or chronic medical condition which could impair the ability of the participant to participate to the study or to comply with the study procedures or interfere with interpretation of study results. * Other concurrent serious illness or medical conditions * Absence of signed and dated participant informed consent form prior to enrollment into the study. * History of hypersensitivity to docetaxel, polysorbate 80 * Known allergies, hypersensitivity or intolerance to prednisone or excipients of abiraterone acetate * Known history of mineralocorticoid excess or deficiency * Inadequate organ and bone marrow function * Contraindications to the use of corticosteroid treatment. * Symptomatic peripheral neuropathy grade \> 1 * Concurrent treatment with strong inducers or strong inhibitors of cytochrome P450 (CYP450) 3A4 * Concurrent treatment with medications metabolized by cytochrome P2D6 (CYP2D6), particularly for those with a small therapeutic window * History of cardiac arrhythmias requiring medical therapy such as atrial fibrillation requiring anticoagulation or digoxin/digitalis; uncontrolled angina pectoris. History of congestive heart failure or myocardial infarction within last 6 months was also not allowed. * Uncontrolled hypertension (systolic BP ≥160 mmHg or diastolic BP ≥ 95 mmHg). Participants with a history of hypertension were allowed, provided that blood pressure was controlled to within these limits by anti-hypertensive treatment * Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 12 months, severe or unstable angina, or New York Heart Association Class III or IV heart disease or cardiac left ventricular ejection fraction measurement of \<50% at baseline * Participants with reproductive potential who did not agree to use accepted and effective method of contraception in conjunction with their partner(s) during the study treatment period. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Maximally Tolerated Dose (MTD) of Cabazitaxel in Combination With Abiraterone Acetate | Up to Cycle 2 of Phase 1 (up to 42 days) | MTD was defined as highest dose level of cabazitaxel in combination with abiraterone acetate at which no more than 1 participant experienced dose limiting toxicities (DLT). DLT was defined as any of the following events related to study treatment: 1) Grade 3 or 4 non-hematological related adverse event with exception of Grade 3 fever without documented infection; Grade 3 nausea, vomiting, or diarrhea in the absence of effective maximal therapy; and Grade 3 hypersensitivity reaction in the absence of required premedication. 2) Hematological toxicity: Febrile neutropenia (fever of unknown origin ≥38.5°C with neutropenia Grade 3 or 4); Neutropenia Grade 4 lasting \>7 days; Thrombocytopenia Grade 4 or Grade 3 complicated by hemorrhage. 3) Re-treatment delay of more than 2 weeks due to delayed recovery from a toxicity related to study treatment to baseline or ≤ Grade 1 (except for alopecia). Grades were based on National Cancer Institute CommonTerminology Criteria for Adverse Events v4.03. |
| Phase 2: Percentage of Participants With Prostate Specific Antigen (PSA) Response | Baseline, every 3 weeks up to PSA progression (maximum duration: 603 days) | Prostate specific antigen (PSA) response was defined as ≥50% decrease from baseline in serum PSA levels, confirmed at least 3 weeks later. Increases of any magnitude during the first 12 weeks were ignored in determining PSA response. PSA was to be measured at baseline, every 3 weeks, throughout study period, until progression. PSA progression was defined as: -An increase of 25% above the nadir (at least 2 ng/mL), confirmed by a second PSA value at least 3 weeks apart, in participants who have achieved a ≥50% decline of PSA. -An increase in PSA by 25 % above the baseline level (at least 2 ng/mL), confirmed by a second PSA value at least 3 weeks apart, in participants who have not achieved a ≥50% decline of PSA. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Percentage of Participants With Objective Response | Baseline, every 12 weeks there after until disease progression (maximum duration: 603 days) | Objective response was defined as having complete response (CR) or Partial Response (PR) assessed by RECIST 1.1. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level and all lymph nodes size was \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters). |
| Phase 2: Overall Survival | From baseline up to death or study cut-off (maximum duration: 603 days) | Overall survival was defined as the time interval from the date of treatment start to the date of death due to any cause. In absence of confirmation of death, survival time was censored at the earlier of the last date the participant was known to be alive and the study cut-off date. Analysis was performed by Kaplan-Meier method. |
| Phase 2: Pharmacokinetic of Cabazitaxel : Maximum Plasma Concentration Observed (Cmax) | 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1 | — |
| Phase 2: Pharmacokinetic of Cabazitaxel : Area Under the Plasma Concentration Versus Time Curve (AUC) | 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1 | Area under the concentration-time curve calculated using the following equation: AUC = Plasma clearance (CL)/dose |
| Phase 2: Pharmacokinetic of Cabazitaxel : Terminal Half-life (t 1/2z) | 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1 | — |
| Phase 2: Objective Progression Free Survival (PFS) | From baseline until radiological tumor or disease progression or death due to any cause, assessed up to Month 5 | Objective PFS was defined as the time interval between the date of enrollment and the first occurrence of any of the events: 1\) Radiological tumor progression (assessed using Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1) was defined as at least a 20 percent increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions. in case of progressive disease (PD) diagnosed only on non target bone lesions on bone scan, PD was to be considered only in case of appearance of at least 2 new lesions on bone scan confirmed 6 weeks later by another bone scan, and at least the appearance of 2 new additional lesions. 2) Death due to any cause. Analysis was performed by Kaplan-Meier method. |
| Phase 2: Pharmacokinetic of Cabazitaxel : Volume of Distribution at Steady State (Vss) | 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1 | — |
| Phase 2: Pharmacokinetic of Abiraterone : Maximum Plasma Concentration Observed (Cmax) | 0 hour (before abiraterone administration); 1, 2, 4, 6, 8, 12, 24 hours post abiraterone administration on Day 1-Cycle 1 | — |
| Phase 2: Pharmacokinetic of Abiraterone : First Time to Reach Cmax (Tmax) | 0 hour (before abiraterone administration); 1, 2, 4, 6, 8, 12, 24 hours post abiraterone administration on Day 1-Cycle 1 | — |
| Phase 2: Pharmacokinetic of Abiraterone : Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC 0-24) | 0 hour (before abiraterone administration); 1, 2, 4, 6, 8, 12, 24 hours post abiraterone administration on Day 1-Cycle 1 | Area under the plasma concentration-time curve calculated using the trapezoidal method from time zero to 24 hours corresponding to abiraterone acetate dosing interval. |
| Phase 2: Pharmacokinetic of Abiraterone : Concentration Observed Just Before Treatment Administration During Repeated Dosing at Steady State (Ctrough ss) | Pre abiraterone dose on Day 1 of Cycle 1 | — |
| Phase 2: Pharmacokinetic of Cabazitaxel : Total Plasma Clearance (CL) | 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1 | — |
| Phase 2: PSA Progression Free Survival | Baseline, every 3 weeks up to PSA progression (maximum duration: 603 days) | Prostate-specific antigen progression-free survival was defined as the time interval between the date of treatment start and the date of either first documented PSA progression or death due to any cause, whichever was earlier. PSA was to be measured at baseline, every 3 weeks, throughout study period, until progression. PSA progression was defined as: -An increase of 25% above the nadir (at least 2 ng/mL), confirmed by a second PSA value at least 3 weeks apart, in participants who have achieved a ≥50% decline of PSA. -An increase in PSA by 25 % above the baseline level (at least 2 ng/mL), confirmed by a second PSA value at least 3 weeks apart, in participants who have not achieved a ≥50% decline of PSA. Analysis was performed by Kaplan Meire method. |
Countries
France, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at 2 centers in phase 1 part and 3 centers in phase 2 part between March 2012 and April 2014.
Pre-assignment details
Phase I was a dose escalation part of Cabazitaxel, administered with a constant dose of abiraterone, to determine maximally tolerated dose. Phase 2 was efficacy and safety evaluation of Cabazitaxel at a dose, determined in Phase 1, in combination with abiraterone.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: Cabazitaxel 20 mg/m^2 + Abiraterone 1000 mg Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal. | 3 |
| Phase 1: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal. | 7 |
| Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg Cabazitaxel at MTD as determined in phase 1 part (25 mg/m\^2) IV infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal. | 27 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Phase 1 | Other | 0 | 1 | 0 |
| Phase 2 | Other | 0 | 0 | 9 |
Baseline characteristics
| Characteristic | Phase 1: Cabazitaxel 20 mg/m^2 + Abiraterone 1000 mg | Phase 1: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg | Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 71.0 years STANDARD_DEVIATION 7 | 60.0 years STANDARD_DEVIATION 10 | 67.1 years STANDARD_DEVIATION 5.4 | 66.1 years STANDARD_DEVIATION 7.1 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 7 Participants | 27 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 7 / 7 | 27 / 27 |
| serious Total, serious adverse events | 3 / 3 | 4 / 7 | 21 / 27 |
Outcome results
Primary
Phase 1: Maximally Tolerated Dose (MTD) of Cabazitaxel in Combination With Abiraterone Acetate
MTD was defined as highest dose level of cabazitaxel in combination with abiraterone acetate at which no more than 1 participant experienced dose limiting toxicities (DLT). DLT was defined as any of the following events related to study treatment: 1) Grade 3 or 4 non-hematological related adverse event with exception of Grade 3 fever without documented infection; Grade 3 nausea, vomiting, or diarrhea in the absence of effective maximal therapy; and Grade 3 hypersensitivity reaction in the absence of required premedication. 2) Hematological toxicity: Febrile neutropenia (fever of unknown origin ≥38.5°C with neutropenia Grade 3 or 4); Neutropenia Grade 4 lasting \>7 days; Thrombocytopenia Grade 4 or Grade 3 complicated by hemorrhage. 3) Re-treatment delay of more than 2 weeks due to delayed recovery from a toxicity related to study treatment to baseline or ≤ Grade 1 (except for alopecia). Grades were based on National Cancer Institute CommonTerminology Criteria for Adverse Events v4.03.
Time frame: Up to Cycle 2 of Phase 1 (up to 42 days)
Population: Analysis was performed on DLT evaluable population defined as all participants who received the first 2 cycles, unless they discontinued the study drug during the first 2 cycles for a DLT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Overall Population | Phase 1: Maximally Tolerated Dose (MTD) of Cabazitaxel in Combination With Abiraterone Acetate | 25 mg/m^2 |
Primary
Phase 2: Percentage of Participants With Prostate Specific Antigen (PSA) Response
Prostate specific antigen (PSA) response was defined as ≥50% decrease from baseline in serum PSA levels, confirmed at least 3 weeks later. Increases of any magnitude during the first 12 weeks were ignored in determining PSA response. PSA was to be measured at baseline, every 3 weeks, throughout study period, until progression. PSA progression was defined as: -An increase of 25% above the nadir (at least 2 ng/mL), confirmed by a second PSA value at least 3 weeks apart, in participants who have achieved a ≥50% decline of PSA. -An increase in PSA by 25 % above the baseline level (at least 2 ng/mL), confirmed by a second PSA value at least 3 weeks apart, in participants who have not achieved a ≥50% decline of PSA.
Time frame: Baseline, every 3 weeks up to PSA progression (maximum duration: 603 days)
Population: Analysis was performed on efficacy/activity population included all participants who had received at least 2 cycles of the study drug in Phase 2, and had a baseline and at least one post-baseline assessment for the efficacy variable of interest.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Overall Population | Phase 2: Percentage of Participants With Prostate Specific Antigen (PSA) Response | 46.2 percentage of participants |
Secondary
Phase 2: Objective Progression Free Survival (PFS)
Objective PFS was defined as the time interval between the date of enrollment and the first occurrence of any of the events: 1\) Radiological tumor progression (assessed using Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1) was defined as at least a 20 percent increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions. in case of progressive disease (PD) diagnosed only on non target bone lesions on bone scan, PD was to be considered only in case of appearance of at least 2 new lesions on bone scan confirmed 6 weeks later by another bone scan, and at least the appearance of 2 new additional lesions. 2) Death due to any cause. Analysis was performed by Kaplan-Meier method.
Time frame: From baseline until radiological tumor or disease progression or death due to any cause, assessed up to Month 5
Population: Analysis was performed on efficacy/activity population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Overall Population | Phase 2: Objective Progression Free Survival (PFS) | NA months |
Secondary
Phase 2: Overall Survival
Overall survival was defined as the time interval from the date of treatment start to the date of death due to any cause. In absence of confirmation of death, survival time was censored at the earlier of the last date the participant was known to be alive and the study cut-off date. Analysis was performed by Kaplan-Meier method.
Time frame: From baseline up to death or study cut-off (maximum duration: 603 days)
Population: Analysis was performed on efficacy/activity population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Overall Population | Phase 2: Overall Survival | NA months |
Secondary
Phase 2: Percentage of Participants With Objective Response
Objective response was defined as having complete response (CR) or Partial Response (PR) assessed by RECIST 1.1. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level and all lymph nodes size was \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters).
Time frame: Baseline, every 12 weeks there after until disease progression (maximum duration: 603 days)
Population: Efficacy/activity population. Number of participants analyzed=participants with measurable disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Overall Population | Phase 2: Percentage of Participants With Objective Response | 21.4 percentage of participants |
Secondary
Phase 2: Pharmacokinetic of Abiraterone : Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC 0-24)
Area under the plasma concentration-time curve calculated using the trapezoidal method from time zero to 24 hours corresponding to abiraterone acetate dosing interval.
Time frame: 0 hour (before abiraterone administration); 1, 2, 4, 6, 8, 12, 24 hours post abiraterone administration on Day 1-Cycle 1
Population: Analysis was performed on PK population. One participant was excluded from analysis due to aberrant data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: Overall Population | Phase 2: Pharmacokinetic of Abiraterone : Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC 0-24) | 928 ng*h/mL | Standard Deviation 466 |
Secondary
Phase 2: Pharmacokinetic of Abiraterone : Concentration Observed Just Before Treatment Administration During Repeated Dosing at Steady State (Ctrough ss)
Time frame: Pre abiraterone dose on Day 1 of Cycle 1
Population: Analysis was performed on PK population. One participant was excluded from analysis due to aberrant data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: Overall Population | Phase 2: Pharmacokinetic of Abiraterone : Concentration Observed Just Before Treatment Administration During Repeated Dosing at Steady State (Ctrough ss) | 9.99 ng/mL | Standard Deviation 13 |
Secondary
Phase 2: Pharmacokinetic of Abiraterone : First Time to Reach Cmax (Tmax)
Time frame: 0 hour (before abiraterone administration); 1, 2, 4, 6, 8, 12, 24 hours post abiraterone administration on Day 1-Cycle 1
Population: Analysis was performed on PK population. One participant was excluded from analysis due to aberrant data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Overall Population | Phase 2: Pharmacokinetic of Abiraterone : First Time to Reach Cmax (Tmax) | 2.00 hour |
Secondary
Phase 2: Pharmacokinetic of Abiraterone : Maximum Plasma Concentration Observed (Cmax)
Time frame: 0 hour (before abiraterone administration); 1, 2, 4, 6, 8, 12, 24 hours post abiraterone administration on Day 1-Cycle 1
Population: Analysis was performed on PK population. One participant was excluded from analysis due to aberrant data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: Overall Population | Phase 2: Pharmacokinetic of Abiraterone : Maximum Plasma Concentration Observed (Cmax) | 216 ng/mL | Standard Deviation 152 |
Secondary
Phase 2: Pharmacokinetic of Cabazitaxel : Area Under the Plasma Concentration Versus Time Curve (AUC)
Area under the concentration-time curve calculated using the following equation: AUC = Plasma clearance (CL)/dose
Time frame: 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1
Population: Analysis was performed on PK population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: Overall Population | Phase 2: Pharmacokinetic of Cabazitaxel : Area Under the Plasma Concentration Versus Time Curve (AUC) | 817 ng*h/mL | Standard Deviation 117 |
Secondary
Phase 2: Pharmacokinetic of Cabazitaxel : Maximum Plasma Concentration Observed (Cmax)
Time frame: 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1
Population: Analysis was performed on pharmacokinetic (PK) population which included all participants who received at least 1 treatment. Pre-dose samples from 3 participants of Phase 2, were above lower limit of quantification (LLOQ) (1.00 ng/mL). Hence, those participants were excluded from analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: Overall Population | Phase 2: Pharmacokinetic of Cabazitaxel : Maximum Plasma Concentration Observed (Cmax) | 330 ng/mL | Standard Deviation 187 |
Secondary
Phase 2: Pharmacokinetic of Cabazitaxel : Terminal Half-life (t 1/2z)
Time frame: 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1
Population: Analysis was performed on PK population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: Overall Population | Phase 2: Pharmacokinetic of Cabazitaxel : Terminal Half-life (t 1/2z) | 91.6 hour | Standard Deviation 62.6 |
Secondary
Phase 2: Pharmacokinetic of Cabazitaxel : Total Plasma Clearance (CL)
Time frame: 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1
Population: Analysis was performed on PK population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: Overall Population | Phase 2: Pharmacokinetic of Cabazitaxel : Total Plasma Clearance (CL) | 31.4 L/h/m^2 | Standard Deviation 4.67 |
Secondary
Phase 2: Pharmacokinetic of Cabazitaxel : Volume of Distribution at Steady State (Vss)
Time frame: 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1
Population: Analysis was performed on PK population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: Overall Population | Phase 2: Pharmacokinetic of Cabazitaxel : Volume of Distribution at Steady State (Vss) | 2711 L/m^2 | Standard Deviation 2493 |
Secondary
Phase 2: PSA Progression Free Survival
Prostate-specific antigen progression-free survival was defined as the time interval between the date of treatment start and the date of either first documented PSA progression or death due to any cause, whichever was earlier. PSA was to be measured at baseline, every 3 weeks, throughout study period, until progression. PSA progression was defined as: -An increase of 25% above the nadir (at least 2 ng/mL), confirmed by a second PSA value at least 3 weeks apart, in participants who have achieved a ≥50% decline of PSA. -An increase in PSA by 25 % above the baseline level (at least 2 ng/mL), confirmed by a second PSA value at least 3 weeks apart, in participants who have not achieved a ≥50% decline of PSA. Analysis was performed by Kaplan Meire method.
Time frame: Baseline, every 3 weeks up to PSA progression (maximum duration: 603 days)
Population: Analysis was performed on efficacy/activity population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Overall Population | Phase 2: PSA Progression Free Survival | 6.93 months |