Metastatic Pancreatic Cancer
Conditions
Keywords
Metastatic Pancreatic Cancer, Abraxane, Gemcitabine
Brief summary
To determine the maximum tolerated dose and dose-limiting toxicity of Gemcitabine plus Albumin-bound paclitaxel (ABI-007) in patients with advanced metastatic pancreatic cancer.
Detailed description
Albumin-bound paclitaxel is a novel, solvent-free, albumin-bound, 130 nanometer particle form of paclitaxel designed to avoid the problems associated with solvents used in Taxol(Abraxane prescribing information 2005). Albumin has a number of properties that make it an attractive molecule to combine with paclitaxel. Albumin is a natural transporter of endogenous hydrophobic molecules such as water-insoluble vitamins and hormones (Vorum 1999)and albumin binding to the gp-60 receptor (albondin) initiates the caveolae-mediated endothelial transport of protein-bound and unbound plasma constituents (John et al 2003, Minshall et al 2003, Tiruppathi et al 1997). This study consisted of a Phase 1 dose escalation phase, a Phase 2 treatment phase and a 24-month follow-up phase.
Interventions
DRUGGemcitabine
Administered by intravenous infusion over 30 minutes.
DRUGAlbumin-bound paclitaxel
Administered by intravenous infusion over 30 minutes.
Sponsors
Celgene
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. Patients with islet cell neoplasms are excluded. * Male or non-pregnant and non-lactating female, and age greater or equal to 18. * If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative serum pregnancy test beta-human chorionic gonadotropin (B-hCG) documented within 72 hours of the first administration of study drug. * If sexually active, the patient must agree to use contraception considered adequate and appropriate by the investigator. * Patient must have received no prior therapy for the treatment of metastatic disease. Prior treatment with 5-fluorouracil (5-FU) or gemcitabine administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed. If a patient received gemcitabine in the adjuvant setting, tumor recurrence must have occurred at least 6 months after completing the last dose of gemcitabine. * Patient has the following blood counts at baseline * Absolute neutrophil count (ANC) equal or greater to 1.5 x 10\^9/L; * Platelets equal or greater to 100 x 10\^9/L * Hemoglobin equal or greater to 9 g/dL. * Patient has the following blood chemistry levels at baseline: * Aspartate aminotransferase (SGOT), Alanine aminotransferase (SGPT) equal or less than 2.5 x upper limit of normal range (ULN) is allowed * Bilirubin less than or equal to ULN * Serum creatinine within normal limits or calculated clearance equal or greater to 60 mL/min/1.73M\^2 patients with serum creatinine levels above the institutional normal value * Patient has no clinically significant abnormalities in urinalysis results * Patient has acceptable coagulation status as indicated by a prothrombin time (PT) within normal limits (plus or minus 15%) and partial thromboplastin time (PTT) within normal limits (plus or minus 15%). * Patient has a Karnofsky performance status (KPS) greater or equal to 70 (Eastern Cooperative Oncology Group \[ECOG\] PS 0-1). * Patient has one or more metastatic tumors measurable by computed tomography (CT) scan. * Patient has been informed about the nature of study, and has agreed to participate in the study, and signed the Informed Consent form prior to participation in any study-related activities.
Exclusion criteria
* Patient has known brain metastases unless previously treated and well controlled for at least 3 months (defined as stable clinically, no edema, no steroids and stable in two scans at least 4 weeks apart). * Patient uses therapeutic coumadin for a history of pulmonary emboli and deep vein thrombosis (DVT). * Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy. * Patient has known infection with human immunodeficiency virus (HIV), hepatitis B, hepatitis C. * Patient has undergone major surgery, other than diagnostic surgery i.e.-- done to obtain a biopsy for diagnosis without removal of an organ), with 4 weeks prior to Day 1 of treatment in this study. * Patient received radiotherapy, surgery, chemotherapy, or an investigational therapy within 3 weeks prior to study entry weeks (6 weeks for nitrosureas or mitomycin C). * Patient has a history of allergy or hypersensitivity to the study drug. * Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug. * Patient is unwilling or unable to comply with study procedures. * Patient is enrolled in any other clinical protocol or investigational trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities | Cycle 1 (Days 1-28) | A dose-limiting toxicity (DLT) is defined as one or more of the following toxicities related to study drug during Cycle 1, according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), Version 3: * Grade 4 neutropenia lasting \>3 days in the absence of growth factor support; * Grade 4 neutropenia associated with fever \>38.5°C; * Any other Grade 4 hematological toxicity; * Grade 3 thrombocytopenia with hemorrhage; * Grade 3 or 4 nausea, vomiting or diarrhea despite prophylaxis or treatment with an optimal anti-emetic or anti-diarrhea regimen; * Any other Grade 3 or higher non-hematological toxicity attributable to the study drug, excluding alopecia and fatigue. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved an Objective Confirmed Overall Response | Up to approximately 4 years | Overall Response is defined as the percent of participants who achieve an objective confirmed complete (CR) or partial response (PR). Response was determined according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, assessed by an Independent Radiological Reviewer. CR: The disappearance of all known disease and no new sites or disease-related symptoms confirmed at least 4 weeks after initial documentation. All sites must be assessed, including non-measurable sites, such as effusions, or markers. PR: At least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 4 weeks after initial documentation and no new non-target lesions and/or unequivocal progression of existing non-target lesions. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing. |
| Percentage of Participants With Disease Control | Up to approximately 4 years | Disease control is defined as participants with Stable Disease for at least 16 weeks, or confirmed complete or partial overall response, based on RECIST guidelines and assessed by an Independent Radiological Reviewer. Stable disease is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for Progressive Disease, and no new non-target lesions or unequivocal progression of existing non-target lesions. Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion. |
| Progression-free Survival | Up to approximately 4 years | Progression-free survival is defined as the time from first dose of study drug to the start of disease progression or patient death, whichever occurs first, assessed by an Independent Radiological Reviewer. Participants who do not have disease progression or have not died were censored at the last known time that the participant was progression free. Progression-free survival was summarized using Kaplan-Meier methods. Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion. |
| Number of Participants With Adverse Events (AE) | Up to 25 months | An AE was any untoward medical occurrence, not necessarily having a causal relationship with the patient's treatment, that began or worsened in grade after the start of study drug through 30 days after the last dose. A serious AE (SAE) is any untoward medical occurrence that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. Treatment-related AEs (TRAEs) include those assessed by the Investigator as possibly, probably, or definitely related to study treatment. Severity was graded according to the NCI CTCAE based on the following: Grade 1- Mild; Grade 2 -Moderate; Grade 3 - Severe; Grade 4 - Life-threatening or disabling; Grade 5 - Death related to AE. |
| Overall Survival | Up to approximately 4 years | Overall survival was defined as the time from the date of first dose of study drug to the date of patient death from all causes. Participants who did not die were censored at the last known time the patient was alive. Patient survival was summarized using Kaplan-Meier methods. |
| Maximal Degree of Myelosuppression | During the treatment phase, up to a maximum of 24 months. | The maximal degree of myelosuppression was assessed by the overall nadir of absolute neutrophil count (ANC), white blood cell count and platelet count based on clinical laboratory measurements. |
| Maximal Degree of Anemia | During the treatment phase, up to a maximum of 24 months. | The maximal degree of anemia (and myelosuppression) was assessed by the overall (any time after first dose of study drug) nadir of hemoglobin levels based on clinical laboratory measurements. |
| Duration of Response | Up to approximately 4 years | Duration of response was assessed by progression-free survival for participants who achieved a confirmed Complete Response or Partial Response, assessed by an Independent Radiological Reviewer. |
Countries
United States
Participant flow
Recruitment details
Enrollment was initiated in November 2006 and completed in September 2008. Sixty-seven patients were enrolled at four sites in the US.
Pre-assignment details
In Phase 1, patients were assigned sequentially to one of the three potential dose levels based on the dose cohort currently enrolling patients (a total of 30 patients). After the maximum tolerated dose (MTD) was determined, all subsequent patients were enrolled at that dose level in Phase 2 (37 patients).
Participants by arm
| Arm | Count |
|---|---|
| 100 mg/m^2 Participants received albumin-bound paclitaxel 100 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity. | 20 |
| 125 mg/m^2 Participants received albumin-bound paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity. | 44 |
| 150 mg/m^2 Participants received albumin-bound paclitaxel 150 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity. | 3 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 | 0 |
| Overall Study | Physician Decision | 1 | 4 | 0 |
| Overall Study | Unacceptable Toxicity | 2 | 8 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 7 | 0 |
Baseline characteristics
| Characteristic | Total | 100 mg/m^2 | 125 mg/m^2 | 150 mg/m^2 |
|---|---|---|---|---|
| Age, Continuous | 62.0 years | 62.0 years | 61.5 years | 69.0 years |
| Current Site(s) of Metastasis/Relapse Abdomen/Peritoneum | 54 participants | 16 participants | 37 participants | 1 participants |
| Current Site(s) of Metastasis/Relapse Axilla | 2 participants | 2 participants | 0 participants | 0 participants |
| Current Site(s) of Metastasis/Relapse Bone | 4 participants | 1 participants | 3 participants | 0 participants |
| Current Site(s) of Metastasis/Relapse Liver | 46 participants | 11 participants | 33 participants | 2 participants |
| Current Site(s) of Metastasis/Relapse Lung/Thoracic | 24 participants | 5 participants | 18 participants | 1 participants |
| Current Site(s) of Metastasis/Relapse Other | 14 participants | 8 participants | 6 participants | 0 participants |
| Current Site(s) of Metastasis/Relapse Pelvis | 5 participants | 1 participants | 3 participants | 1 participants |
| Current Site(s) of Metastasis/Relapse Skin/Soft Tissue | 1 participants | 0 participants | 1 participants | 0 participants |
| Current Site(s) of Metastasis/Relapse Supraclavicular Nodes | 2 participants | 0 participants | 2 participants | 0 participants |
| Dominant Current Site of Metastasis/Relapse Non-visceral | 1 participants | 1 participants | 0 participants | 0 participants |
| Dominant Current Site of Metastasis/Relapse Visceral | 66 participants | 19 participants | 44 participants | 3 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Fully Active) | 33 participants | 9 participants | 22 participants | 2 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Restrictive but Ambulatory) | 34 participants | 11 participants | 22 participants | 1 participants |
| Histology of Primary Diagnosis: Adenocarcinoma | 67 participants | 20 participants | 44 participants | 3 participants |
| Race/Ethnicity, Customized Asian | 2 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Black, of African Heritage | 2 participants | 0 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized Other | 1 participants | 1 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized White, Hispanic, or Latino | 8 participants | 2 participants | 4 participants | 2 participants |
| Race/Ethnicity, Customized White, Non-Hispanic, and Non-Latino | 54 participants | 16 participants | 37 participants | 1 participants |
| Region of Enrollment United States | 67 participants | 20 participants | 44 participants | 3 participants |
| Sex: Female, Male Female | 35 Participants | 9 Participants | 25 Participants | 1 Participants |
| Sex: Female, Male Male | 32 Participants | 11 Participants | 19 Participants | 2 Participants |
| Time from First Documented Metastasis/Relapse to Study Entry | 0.7 months | 0.8 months | 0.7 months | 0.3 months |
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 | 20 / 20 | 44 / 44 | 3 / 3 |
| serious Total, serious adverse events | 10 / 20 | 24 / 44 | 1 / 3 |
Outcome results
Primary
Number of Participants With Dose-limiting Toxicities
A dose-limiting toxicity (DLT) is defined as one or more of the following toxicities related to study drug during Cycle 1, according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), Version 3: * Grade 4 neutropenia lasting \>3 days in the absence of growth factor support; * Grade 4 neutropenia associated with fever \>38.5°C; * Any other Grade 4 hematological toxicity; * Grade 3 thrombocytopenia with hemorrhage; * Grade 3 or 4 nausea, vomiting or diarrhea despite prophylaxis or treatment with an optimal anti-emetic or anti-diarrhea regimen; * Any other Grade 3 or higher non-hematological toxicity attributable to the study drug, excluding alopecia and fatigue.
Time frame: Cycle 1 (Days 1-28)
Population: Phase 1 treated population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg/m^2 | Number of Participants With Dose-limiting Toxicities | 4 participants |
| 125 mg/m^2 | Number of Participants With Dose-limiting Toxicities | 0 participants |
| 150 mg/m^2 | Number of Participants With Dose-limiting Toxicities | 1 participants |
Secondary
Duration of Response
Duration of response was assessed by progression-free survival for participants who achieved a confirmed Complete Response or Partial Response, assessed by an Independent Radiological Reviewer.
Time frame: Up to approximately 4 years
Population: Treated patients with an overall confirmed Complete Response or Partial Response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 mg/m^2 | Duration of Response | NA months |
| 125 mg/m^2 | Duration of Response | 7.3 months |
Secondary
Maximal Degree of Anemia
The maximal degree of anemia (and myelosuppression) was assessed by the overall (any time after first dose of study drug) nadir of hemoglobin levels based on clinical laboratory measurements.
Time frame: During the treatment phase, up to a maximum of 24 months.
Population: Treated patients with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 100 mg/m^2 | Maximal Degree of Anemia | 95.1 g/L | Standard Deviation 12.85 |
| 125 mg/m^2 | Maximal Degree of Anemia | 91.8 g/L | Standard Deviation 10.43 |
| 150 mg/m^2 | Maximal Degree of Anemia | 95.3 g/L | Standard Deviation 15.37 |
Secondary
Maximal Degree of Myelosuppression
The maximal degree of myelosuppression was assessed by the overall nadir of absolute neutrophil count (ANC), white blood cell count and platelet count based on clinical laboratory measurements.
Time frame: During the treatment phase, up to a maximum of 24 months.
Population: Treated patients with available data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 mg/m^2 | Maximal Degree of Myelosuppression | Platelet count | 120.3 x10^9/L | Standard Deviation 79.02 |
| 100 mg/m^2 | Maximal Degree of Myelosuppression | White blood cell count | 2.69 x10^9/L | Standard Deviation 1.734 |
| 100 mg/m^2 | Maximal Degree of Myelosuppression | Absolute neutrophil count | 1.38 x10^9/L | Standard Deviation 1.541 |
| 125 mg/m^2 | Maximal Degree of Myelosuppression | Absolute neutrophil count | 0.96 x10^9/L | Standard Deviation 1.446 |
| 125 mg/m^2 | Maximal Degree of Myelosuppression | Platelet count | 88.3 x10^9/L | Standard Deviation 62.1 |
| 125 mg/m^2 | Maximal Degree of Myelosuppression | White blood cell count | 2.18 x10^9/L | Standard Deviation 1.849 |
| 150 mg/m^2 | Maximal Degree of Myelosuppression | Platelet count | 58.7 x10^9/L | Standard Deviation 48.64 |
| 150 mg/m^2 | Maximal Degree of Myelosuppression | Absolute neutrophil count | 0.47 x10^9/L | Standard Deviation 0.46 |
| 150 mg/m^2 | Maximal Degree of Myelosuppression | White blood cell count | 1.52 x10^9/L | Standard Deviation 1.484 |
Secondary
Number of Participants With Adverse Events (AE)
An AE was any untoward medical occurrence, not necessarily having a causal relationship with the patient's treatment, that began or worsened in grade after the start of study drug through 30 days after the last dose. A serious AE (SAE) is any untoward medical occurrence that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. Treatment-related AEs (TRAEs) include those assessed by the Investigator as possibly, probably, or definitely related to study treatment. Severity was graded according to the NCI CTCAE based on the following: Grade 1- Mild; Grade 2 -Moderate; Grade 3 - Severe; Grade 4 - Life-threatening or disabling; Grade 5 - Death related to AE.
Time frame: Up to 25 months
Population: Treated patients: all enrolled patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 100 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 grade 3 or higher AE | 15 participants |
| 100 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 dose interruption due to AE | 1 participants |
| 100 mg/m^2 | Number of Participants With Adverse Events (AE) | Patients with at least 1 treatment-related SAE | 4 participants |
| 100 mg/m^2 | Number of Participants With Adverse Events (AE) | Patients with at least 1 AE | 20 participants |
| 100 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 dose reduction due to TRAE | 4 participants |
| 100 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 AE and drug permanently discontinued | 3 participants |
| 100 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 treatment-related dose delay due to AE | 13 participants |
| 100 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 TRAE and drug permanently discontinued | 2 participants |
| 100 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 treatment-related AE | 18 participants |
| 100 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 treatment-emergent dose delay due to AE | 14 participants |
| 100 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 treatment-related grade 3 to 5 AE | 11 participants |
| 100 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 AE resulting in death | 0 participants |
| 100 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 treatment-related AE dose interruption | 1 participants |
| 100 mg/m^2 | Number of Participants With Adverse Events (AE) | Patients with at least 1 SAE | 10 participants |
| 125 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 treatment-related AE dose interruption | 0 participants |
| 125 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 TRAE and drug permanently discontinued | 8 participants |
| 125 mg/m^2 | Number of Participants With Adverse Events (AE) | Patients with at least 1 AE | 44 participants |
| 125 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 grade 3 or higher AE | 42 participants |
| 125 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 treatment-related grade 3 to 5 AE | 38 participants |
| 125 mg/m^2 | Number of Participants With Adverse Events (AE) | Patients with at least 1 SAE | 24 participants |
| 125 mg/m^2 | Number of Participants With Adverse Events (AE) | Patients with at least 1 treatment-related SAE | 12 participants |
| 125 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 AE and drug permanently discontinued | 12 participants |
| 125 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 dose reduction due to TRAE | 10 participants |
| 125 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 dose interruption due to AE | 0 participants |
| 125 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 treatment-related AE | 42 participants |
| 125 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 treatment-emergent dose delay due to AE | 27 participants |
| 125 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 treatment-related dose delay due to AE | 27 participants |
| 125 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 AE resulting in death | 1 participants |
| 150 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 AE resulting in death | 1 participants |
| 150 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 dose interruption due to AE | 0 participants |
| 150 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 treatment-related grade 3 to 5 AE | 3 participants |
| 150 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 treatment-related dose delay due to AE | 3 participants |
| 150 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 treatment-related AE dose interruption | 0 participants |
| 150 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 treatment-related AE | 3 participants |
| 150 mg/m^2 | Number of Participants With Adverse Events (AE) | Patients with at least 1 AE | 3 participants |
| 150 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 treatment-emergent dose delay due to AE | 3 participants |
| 150 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 AE and drug permanently discontinued | 2 participants |
| 150 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 TRAE and drug permanently discontinued | 2 participants |
| 150 mg/m^2 | Number of Participants With Adverse Events (AE) | Patients with at least 1 treatment-related SAE | 1 participants |
| 150 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 grade 3 or higher AE | 3 participants |
| 150 mg/m^2 | Number of Participants With Adverse Events (AE) | At least 1 dose reduction due to TRAE | 1 participants |
| 150 mg/m^2 | Number of Participants With Adverse Events (AE) | Patients with at least 1 SAE | 1 participants |
Secondary
Overall Survival
Overall survival was defined as the time from the date of first dose of study drug to the date of patient death from all causes. Participants who did not die were censored at the last known time the patient was alive. Patient survival was summarized using Kaplan-Meier methods.
Time frame: Up to approximately 4 years
Population: Treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 mg/m^2 | Overall Survival | 9.3 months |
| 125 mg/m^2 | Overall Survival | 12.2 months |
| 150 mg/m^2 | Overall Survival | 6.1 months |
Secondary
Percentage of Participants Who Achieved an Objective Confirmed Overall Response
Overall Response is defined as the percent of participants who achieve an objective confirmed complete (CR) or partial response (PR). Response was determined according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, assessed by an Independent Radiological Reviewer. CR: The disappearance of all known disease and no new sites or disease-related symptoms confirmed at least 4 weeks after initial documentation. All sites must be assessed, including non-measurable sites, such as effusions, or markers. PR: At least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 4 weeks after initial documentation and no new non-target lesions and/or unequivocal progression of existing non-target lesions. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing.
Time frame: Up to approximately 4 years
Population: Treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg/m^2 | Percentage of Participants Who Achieved an Objective Confirmed Overall Response | 25 percentage of participants |
| 125 mg/m^2 | Percentage of Participants Who Achieved an Objective Confirmed Overall Response | 39 percentage of participants |
| 150 mg/m^2 | Percentage of Participants Who Achieved an Objective Confirmed Overall Response | 0 percentage of participants |
Secondary
Percentage of Participants With Disease Control
Disease control is defined as participants with Stable Disease for at least 16 weeks, or confirmed complete or partial overall response, based on RECIST guidelines and assessed by an Independent Radiological Reviewer. Stable disease is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for Progressive Disease, and no new non-target lesions or unequivocal progression of existing non-target lesions. Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.
Time frame: Up to approximately 4 years
Population: Treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg/m^2 | Percentage of Participants With Disease Control | 55 percentage of participants |
| 125 mg/m^2 | Percentage of Participants With Disease Control | 55 percentage of participants |
| 150 mg/m^2 | Percentage of Participants With Disease Control | 33 percentage of participants |
Secondary
Progression-free Survival
Progression-free survival is defined as the time from first dose of study drug to the start of disease progression or patient death, whichever occurs first, assessed by an Independent Radiological Reviewer. Participants who do not have disease progression or have not died were censored at the last known time that the participant was progression free. Progression-free survival was summarized using Kaplan-Meier methods. Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.
Time frame: Up to approximately 4 years
Population: Treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 mg/m^2 | Progression-free Survival | 6.1 months |
| 125 mg/m^2 | Progression-free Survival | 6.9 months |
| 150 mg/m^2 | Progression-free Survival | 1.6 months |