Stage IV (Metastatic) Breast Cancer
Conditions
Keywords
Breast cancer
Brief summary
The purpose of this study is to: 1) determine the optimal tolerated dose of ABI-007 and vinorelbine, given concurrently on a weekly basis, in the absence of planned growth factor support with granulocyte colony-stimulating factor (G-CSF) (Patients with HER-2/neu positive disease may receive Herceptin, and 2) determine the optimal tolerated dose of ABI-007 and vinorelbine, given concurrently on a weekly basis, in the presence of planned growth factor support with G-CSF.
Interventions
DRUGABI-007
Weekly intravenous infusions over 30 minutes.
DRUGvinorelbine
Weekly intravenous infusions over 10-30 minutes, immediately after ABI-007. Vinorelbine is commercially available and was not supplied by the Sponsor.
DRUGTrastuzumab
Trastuzumab was administered to participants who had HER-2-neu positive tumors. Participants received trastuzumab by IV infusion via a vascular access device following dosing with ABI-007 and vinorelbine. During their first cycle, 4 mg/kg was administered on day 1 of that cycle as a loading dose. During subsequent weekly treatments, 2 mg/kg was administered. Trastuzumab is commercially available and was not supplied by the Sponsor.
BIOLOGICALG-CSF
During Part 1, participants followed a dosing regimen with ABI-007 and vinorelbine without G-CSF treatment. However, G-CSF was allowed for administration as necessary in accordance with commonly accepted clinical guidelines. In Part 2, participants started G-CSF treatment in concurrence with their ABI-007 and vinorelbine treatments. G-CSF was administered to all participants on Days 2-7 of each cycle, at a dose of 5 mcg/kg. If the participant's absolute neutrophil (ANC) count was \>20,000/mm\^3 on the day of anticipated chemotherapy, the site staff reduced the daily dose of G-CSF by 50% to 2.5 mcg/kg. G-CSF is commercially available and was not supplied by the Sponsor.
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 microscopically confirmed invasive breast carcinoma with clinical and/or radiographic evidence of stage 4 disease. If diagnosis is based on pleural effusion, positive cytology must be confirmed. * Patient has had no prior chemotherapy for Stage 4 disease (hormone therapy is permitted). Prior adjuvant paclitaxel by 3-hour infusion is permitted, if there is no residual neuropathy. Prior adjuvant docetaxel on an every 3 week schedule is permitted. * Disease must be measurable (unidimensional by Response Evaluation Criteria In Solid Tumors (RECIST) criteria) or evaluable (e.g., malignant effusion, marrow involvement). Elevated tumor markers alone are insufficient. * Age \>18. * Southwest Oncology Group (SWOG)/Eastern Oncology Group (ECOG) performance status must be \< or =2 at screen and on treatment day one. * Life expectancy must be estimated at \>16 weeks. * Prior irradiation is permitted, provided: * Does not exceed 25% of the estimated bone marrow volume * Measurable/evaluable disease exists outside the radiation field, or progressive disease is documented within the radiation field. * Informed consent must be obtained prior to registration. * Patients must be \> 2 weeks from prior surgery; \> 3 weeks from radiation therapy to the pelvis, spine or long bones; \> 3 weeks from prior chemotherapy (\> 6 weeks for mitomycin C or nitrosureas), or \> 2 weeks from prior hormonal therapy. * All patients must have placement of appropriate central venous access device. * Tumor HER2/neu expression must be determined prior to study enrollment. Assessment may be by fluorescence in situ hybridization (FISH) assay or by immunohistochemistry (ICC). If determination is intermediate by ICC, FISH must be performed. For enrollment purposes, this phase I study will not discriminate based on HER2 status. However, documentation of patients' HER2 status will be maintained and Herceptin will be prescribed for all HER2 positive patients.
Exclusion criteria
* Granulocytes \< 1,500/mm\^3. * Platelets \< 100,000/mm\^3. * Hemoglobin \< 9 gm/dl. * Creatinine \> 2.0 mg/dl. * Total bilirubin \> 2 mg/dl. * Visceral crisis characterized by rapidly progressive hepatic or lymphangitic lung metastases. * Medically unstable as judged by the patient's physician. * Pregnancy or lactation; failure to employ adequate contraception. * Uncontrolled central nervous system (CNS) disease. * Pre-existing Grade ≥ 2 peripheral neuropathy except for abnormalities due to cancer. * Psychological, familial, sociological or geographical conditions which do not permit weekly medical follow-up and compliance with the study protocol. * Prior therapy with vinorelbine or prior therapy with a taxane that resulted in neuropathy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nadir Measurement for Hemoglobin (Hgb) | up to week 129 (longest treatment) | Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest observed measurement is the nadir. Blood counts were performed each week of treatment. |
| Participants With Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) | up to month 30 | Overall response rate (ORR) is complete response (CR) + partial response (PR). Complete response (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. Disappearance of all non-target lesions. The normalization of tumor marker level confirmed at least 4 weeks after initial documentation. Partial response (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. 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. As well as persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. |
| Participants With Dose Limiting Toxicities | up to month 1 | Toxicities were evaluated based on the U.S. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Any drug-related toxicities CTC Grade 3 or higher were considered dose limiting. Grade 3=severe AE, Grade 4=life-threatening or disabling AE, Grade 5=death. Other conditions considered dose-limiting toxicities include: * requirement of a dose adjustment during the first 4 weeks * a dose delay of \>3 weeks during the first 4 weeks Grade 3 or greater toxicities attributed to the use of Herceptin were not considered dose-limiting toxicities. The optimal tolerated dose of ABI-007 and vinorelbine given concurrently was defined as the dose administered in the absence of DLTs. |
| Percentage of Participants With Discontinued, Delayed or Interrupted Therapy | up to week 129 | Percentage of participants who had discontinued therapy or had a delayed dose or an interrupted (omitted) dose due to toxicities/adverse events. |
| Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | up to week 129 (longest treatment) | Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) blood counts were graded using NCI CTCAE version 3. ANC: Grade 0 = within normal limits; Grade 1 = \< lower limit of normal - 1.5\*10\^9/L; Grade 2 = \<1.5 - 1.0\*10\^9/L; Grade 3 = \<1.0 - 0.5\*10\^9/L; Grade 4 = \<0.5\*10\^9/L WBC: Grade 0 = within normal limits; Grade 1 = \< lower limit of normal - 3.0\*10\^9/L; Grade 2 = \<3.0 - 2.0\*10\^9/L; Grade 3 = \<2.0 - 1.0\*10\^9/L; Grade 4 = \<1.0\*10\^9/L Platelets: Grade 0 = within normal limits; Grade 1 = \< lower limit of normal - 75.0\*10\^9/L; Grade 2 = \<75.0 - 50.0\*10\^9/L; Grade 3 = \<50.0 - 25.0\*10\^9/L; Grade 4 = \<25.0\*10\^9/L Hemoglobin: Grade 0 = within normal limits; Grade 1 = \< lower limit of normal - 100 g/L ; Grade 2 = \<100 - 80 g/L; Grade 3 = \<80 - 65 g/L; Grade 4 = \<65 g/L |
| Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count | up to week 129 (longest treatment) | Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest observed measurement is the nadir. Blood counts were performed each week of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan Meier Estimate for Time to Disease Progression (TTP) | up to month 30 | Time to progression was defined as the time from the first dose of study drug to the start of progression. Participants that did not have progression were censored at the last known time the patient was evaluated for progression. Participants that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Progressive disease was defined as at least a 20% increase in the sum of the longest diameters of target lesions; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion. |
| Kaplan-Meier Estimate for Duration of Response | up to month 30 | Duration of response is defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or patient death from any cause, whichever occurred first. Patients that did not have progression or have not died were censored at the last known time the patient was progression free. Patients that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Complete response (CR) and partial response (PR) are defined in outcome #1. Progressive disease was defined as at least a 20% increase in the sum of the longest diameters of target lesions; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion. |
| Kaplan Meier Estimate for Progression-Free Survival (PFS) | up to month 30 | PFS was defined as the time from the first dose of study drug to the start of progression or patient death (any cause) whichever occurred first. Participants that did not have progression or have not died were censored at the last known time the participant was progression free. Participants that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Because no patients died as a result of a non-disease progression event, the analysis of PFS was identical to the analysis for TTP. |
| Kaplan-Meier Estimates for Participant Survival | up to 39 months | Participant survival is the time from the first dose of study drug to participant death from any cause. Participants that did not die were censored at the last known time the participant was alive. |
| Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) | up to month 30 | Disease control is stable disease (SD) for \>=16 weeks + complete response (CR) + partial response (PR). See Outcome #1 for definitions of CR and PR. RECIST defines SD for target lesions as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, no occurrence of progression disease for non-target lesions, and no new lesions. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned. | 4 |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given. | 6 |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given. | 6 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 1 | 1 | 0 |
| Overall Study | Unacceptable toxicity | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Total | Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Part 2: 90 mg ABI-007 + 20 mg Vinorelbine |
|---|---|---|---|---|
| Age, Customized < 65 years | 5 participants 12.6 | 14 participants | 4 participants 5.74 | 5 participants 12.23 |
| Age, Customized >= 65 years | 1 participants | 2 participants | 0 participants | 1 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Status 0 (Asymptomatic) | 2 participants | 4 participants | 1 participants | 1 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Status 1 (Symptomatic but completely ambulatory) | 4 participants | 11 participants | 3 participants | 4 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Status 2 (Ambulatory but unable to work) | 0 participants | 1 participants | 0 participants | 1 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Status 3 (Limited self-care) | 0 participants | 0 participants | 0 participants | 0 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Status 4 (Completely disabled) | 0 participants | 0 participants | 0 participants | 0 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Status 5 (Death) | 0 participants | 0 participants | 0 participants | 0 participants |
| Menopausal Status Post-menopausal | 4 participants | 12 participants | 3 participants | 5 participants |
| Menopausal Status Pre-menopausal | 2 participants | 4 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized White, Hispanic or Latino | 1 participants | 3 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized White, Non-Hispanic and Non-Latino | 5 participants | 12 participants | 3 participants | 4 participants |
| Sex: Female, Male Female | 6 Participants | 16 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Smoking Status Current Smoker | 1 participants | 2 participants | 1 participants | 0 participants |
| Smoking Status Never Smoked | 4 participants | 9 participants | 2 participants | 3 participants |
| Smoking Status Previous Smoker, but have Stopped | 1 participants | 5 participants | 1 participants | 3 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 10 | 6 / 6 |
| serious Total, serious adverse events | 5 / 10 | 1 / 6 |
Outcome results
Primary
Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count
Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest observed measurement is the nadir. Blood counts were performed each week of treatment.
Time frame: up to week 129 (longest treatment)
Population: Treated population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count | WBC | 2.79 10^9/L | Standard Deviation 0.999 |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count | ANC | 1.74 10^9/L | Standard Deviation 1.444 |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count | Platelets | 221.5 10^9/L | Standard Deviation 108.19 |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count | WBC | 2.56 10^9/L | Standard Deviation 0.962 |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count | ANC | 1.00 10^9/L | Standard Deviation 0.864 |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count | Platelets | 187.2 10^9/L | Standard Deviation 70.35 |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count | ANC | 1.72 10^9/L | Standard Deviation 1.589 |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count | Platelets | 222.7 10^9/L | Standard Deviation 50.11 |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count | WBC | 2.92 10^9/L | Standard Deviation 1.572 |
Primary
Nadir Measurement for Hemoglobin (Hgb)
Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest observed measurement is the nadir. Blood counts were performed each week of treatment.
Time frame: up to week 129 (longest treatment)
Population: Treated population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Nadir Measurement for Hemoglobin (Hgb) | 89.3 g/L | Standard Deviation 16.11 |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Nadir Measurement for Hemoglobin (Hgb) | 89.7 g/L | Standard Deviation 14.53 |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Nadir Measurement for Hemoglobin (Hgb) | 83.5 g/L | Standard Deviation 6.09 |
Primary
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)
Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) blood counts were graded using NCI CTCAE version 3. ANC: Grade 0 = within normal limits; Grade 1 = \< lower limit of normal - 1.5\*10\^9/L; Grade 2 = \<1.5 - 1.0\*10\^9/L; Grade 3 = \<1.0 - 0.5\*10\^9/L; Grade 4 = \<0.5\*10\^9/L WBC: Grade 0 = within normal limits; Grade 1 = \< lower limit of normal - 3.0\*10\^9/L; Grade 2 = \<3.0 - 2.0\*10\^9/L; Grade 3 = \<2.0 - 1.0\*10\^9/L; Grade 4 = \<1.0\*10\^9/L Platelets: Grade 0 = within normal limits; Grade 1 = \< lower limit of normal - 75.0\*10\^9/L; Grade 2 = \<75.0 - 50.0\*10\^9/L; Grade 3 = \<50.0 - 25.0\*10\^9/L; Grade 4 = \<25.0\*10\^9/L Hemoglobin: Grade 0 = within normal limits; Grade 1 = \< lower limit of normal - 100 g/L ; Grade 2 = \<100 - 80 g/L; Grade 3 = \<80 - 65 g/L; Grade 4 = \<65 g/L
Time frame: up to week 129 (longest treatment)
Population: Treated population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Platelets: grade 0 | 4 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | ANC: grade 2 | 0 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | WBC: grade 2 | 1 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | WBC: grade 3 | 1 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | WBC: grade 4 | 0 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Platelets: grade 2 | 0 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Platelets: grade 4 | 0 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Hemoglobin: grade 2 | 1 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Hemoglobin: grade 3 | 1 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Hemoglobin: grade 4 | 0 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | ANC: grade 0 | 1 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | ANC: grade 1 | 1 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | ANC: grade 3 | 2 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | ANC: grade 4 | 0 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | WBC: grade 0 | 2 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | WBC: grade 1 | 0 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Platelets: grade 1 | 0 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Platelets: grade 3 | 0 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Hemoglobin: grade 0 | 0 participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Hemoglobin: grade 1 | 2 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Platelets: grade 2 | 1 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Platelets: grade 3 | 0 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Platelets: grade 4 | 0 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Hemoglobin: grade 0 | 1 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Hemoglobin: grade 2 | 3 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Hemoglobin: grade 3 | 2 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Hemoglobin: grade 4 | 0 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | WBC: grade 3 | 2 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | ANC: grade 0 | 1 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | ANC: grade 1 | 1 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | ANC: grade 2 | 1 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | ANC: grade 3 | 0 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | WBC: grade 0 | 3 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | WBC: grade 1 | 0 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Hemoglobin: grade 1 | 0 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | WBC: grade 2 | 1 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | WBC: grade 4 | 0 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Platelets: grade 0 | 4 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Platelets: grade 1 | 1 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | ANC: grade 4 | 3 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | WBC: grade 2 | 2 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | ANC: grade 2 | 0 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Platelets: grade 3 | 0 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Hemoglobin: grade 1 | 0 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | ANC: grade 3 | 1 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Platelets: grade 1 | 0 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Hemoglobin: grade 0 | 0 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | WBC: grade 0 | 1 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | ANC: grade 4 | 2 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Hemoglobin: grade 2 | 4 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Platelets: grade 4 | 0 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Platelets: grade 0 | 6 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Hemoglobin: grade 3 | 2 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | WBC: grade 1 | 1 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | WBC: grade 4 | 0 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Hemoglobin: grade 4 | 0 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | ANC: grade 1 | 0 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | Platelets: grade 2 | 0 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | ANC: grade 0 | 3 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) | WBC: grade 3 | 2 participants |
Primary
Participants With Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0)
Overall response rate (ORR) is complete response (CR) + partial response (PR). Complete response (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. Disappearance of all non-target lesions. The normalization of tumor marker level confirmed at least 4 weeks after initial documentation. Partial response (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. 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. As well as persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits.
Time frame: up to month 30
Population: Treated population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participants With Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) | 25 percentage of participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participants With Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) | 16.7 percentage of participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participants With Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) | 33.3 percentage of participants |
Primary
Participants With Dose Limiting Toxicities
Toxicities were evaluated based on the U.S. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Any drug-related toxicities CTC Grade 3 or higher were considered dose limiting. Grade 3=severe AE, Grade 4=life-threatening or disabling AE, Grade 5=death. Other conditions considered dose-limiting toxicities include: * requirement of a dose adjustment during the first 4 weeks * a dose delay of \>3 weeks during the first 4 weeks Grade 3 or greater toxicities attributed to the use of Herceptin were not considered dose-limiting toxicities. The optimal tolerated dose of ABI-007 and vinorelbine given concurrently was defined as the dose administered in the absence of DLTs.
Time frame: up to month 1
Population: Treated population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Participants With Dose Limiting Toxicities | 2 participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Participants With Dose Limiting Toxicities | 2 participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Participants With Dose Limiting Toxicities | 2 participants |
Primary
Percentage of Participants With Discontinued, Delayed or Interrupted Therapy
Percentage of participants who had discontinued therapy or had a delayed dose or an interrupted (omitted) dose due to toxicities/adverse events.
Time frame: up to week 129
Population: Treated population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Discontinued, Delayed or Interrupted Therapy | At least 1 Vinorelbine dose interruption | 0 percentage of participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Discontinued, Delayed or Interrupted Therapy | At least 1 Vinorelbine dose reduction | 50 percentage of participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Discontinued, Delayed or Interrupted Therapy | At least 1 ABI-007 dose reduction | 50 percentage of participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Discontinued, Delayed or Interrupted Therapy | At least 1 therapy delay | 75 percentage of participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Discontinued, Delayed or Interrupted Therapy | At least 1 ABI-007 dose interruption | 0 percentage of participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Discontinued, Delayed or Interrupted Therapy | At least 1 Vinorelbine dose reduction | 50 percentage of participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Discontinued, Delayed or Interrupted Therapy | At least 1 ABI-007 dose interruption | 0 percentage of participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Discontinued, Delayed or Interrupted Therapy | At least 1 ABI-007 dose reduction | 50 percentage of participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Discontinued, Delayed or Interrupted Therapy | At least 1 Vinorelbine dose interruption | 0 percentage of participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Discontinued, Delayed or Interrupted Therapy | At least 1 therapy delay | 83 percentage of participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Percentage of Participants With Discontinued, Delayed or Interrupted Therapy | At least 1 therapy delay | 67 percentage of participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Percentage of Participants With Discontinued, Delayed or Interrupted Therapy | At least 1 Vinorelbine dose interruption | 0 percentage of participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Percentage of Participants With Discontinued, Delayed or Interrupted Therapy | At least 1 Vinorelbine dose reduction | 17 percentage of participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Percentage of Participants With Discontinued, Delayed or Interrupted Therapy | At least 1 ABI-007 dose interruption | 0 percentage of participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Percentage of Participants With Discontinued, Delayed or Interrupted Therapy | At least 1 ABI-007 dose reduction | 17 percentage of participants |
Secondary
Kaplan-Meier Estimate for Duration of Response
Duration of response is defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or patient death from any cause, whichever occurred first. Patients that did not have progression or have not died were censored at the last known time the patient was progression free. Patients that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Complete response (CR) and partial response (PR) are defined in outcome #1. Progressive disease was defined as at least a 20% increase in the sum of the longest diameters of target lesions; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.
Time frame: up to month 30
Population: Treated participants who had a response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Kaplan-Meier Estimate for Duration of Response | 10.4 months |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Kaplan-Meier Estimate for Duration of Response | 7.9 months |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Kaplan-Meier Estimate for Duration of Response | 9.6 months |
Secondary
Kaplan Meier Estimate for Progression-Free Survival (PFS)
PFS was defined as the time from the first dose of study drug to the start of progression or patient death (any cause) whichever occurred first. Participants that did not have progression or have not died were censored at the last known time the participant was progression free. Participants that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Because no patients died as a result of a non-disease progression event, the analysis of PFS was identical to the analysis for TTP.
Time frame: up to month 30
Population: Treated population of participants who had disease progression or who died
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Kaplan Meier Estimate for Progression-Free Survival (PFS) | 8.8 months |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Kaplan Meier Estimate for Progression-Free Survival (PFS) | 7.9 months |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Kaplan Meier Estimate for Progression-Free Survival (PFS) | 4.2 months |
Secondary
Kaplan Meier Estimate for Time to Disease Progression (TTP)
Time to progression was defined as the time from the first dose of study drug to the start of progression. Participants that did not have progression were censored at the last known time the patient was evaluated for progression. Participants that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Progressive disease was defined as at least a 20% increase in the sum of the longest diameters of target lesions; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.
Time frame: up to month 30
Population: Treated population of participants with disease progression
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Kaplan Meier Estimate for Time to Disease Progression (TTP) | 8.8 months |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Kaplan Meier Estimate for Time to Disease Progression (TTP) | 7.9 months |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Kaplan Meier Estimate for Time to Disease Progression (TTP) | 4.2 months |
Secondary
Kaplan-Meier Estimates for Participant Survival
Participant survival is the time from the first dose of study drug to participant death from any cause. Participants that did not die were censored at the last known time the participant was alive.
Time frame: up to 39 months
Population: Treated population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Kaplan-Meier Estimates for Participant Survival | 32.7 months |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Kaplan-Meier Estimates for Participant Survival | 29.2 months |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Kaplan-Meier Estimates for Participant Survival | 22.2 months |
Secondary
Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0)
Disease control is stable disease (SD) for \>=16 weeks + complete response (CR) + partial response (PR). See Outcome #1 for definitions of CR and PR. RECIST defines SD for target lesions as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, no occurrence of progression disease for non-target lesions, and no new lesions.
Time frame: up to month 30
Population: Treated population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) | Disease control | 75 percentage of participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) | Complete response | 0 percentage of participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) | Partial response | 25 percentage of participants |
| Part 1: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) | Stable disease >=16 weeks | 50 percentage of participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) | Complete response | 0 percentage of participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) | Stable disease >=16 weeks | 50 percentage of participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) | Disease control | 66.7 percentage of participants |
| Part 2: 80 mg ABI-007 + 15 mg Vinorelbine | Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) | Partial response | 17 percentage of participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) | Partial response | 33 percentage of participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) | Complete response | 0 percentage of participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) | Disease control | 33.3 percentage of participants |
| Part 2: 90 mg ABI-007 + 20 mg Vinorelbine | Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) | Stable disease >=16 weeks | 0 percentage of participants |