A Phase 2/3, Multi-Center, Open-Label, Randomized Study of Weekly Nab®-Paclitaxel in Combination With Gemcitabine or Carboplatin, Compared to Gemcitabine/Carboplatin, as First Line Treatment in Subjects With ER, PgR, and HER2 Negative (Triple Negative) Metastatic Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- nab-Paclitaxel
- Conditions
- Breast Tumor
- Sponsor
- Celgene
- Enrollment
- 191
- Locations
- 138
- Primary Endpoint
- Kaplan-Meier Estimates of Progression-Free Survival (PFS) Based on Investigator Assessment.
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
The purpose of this study is to compare the safety and efficacy of nab-paclitaxel in combination with either gemcitabine or carboplatin to the combination of gemcitabine and carboplatin as first line treatment in female subjects with triple negative metastatic breast cancer (TNMBC) or metastatic triple negative breast cancer.
Detailed Description
ABI-007-MBC- 001 is a Phase 2/3, multicenter, open-label, randomized, study that will compare the safety and efficacy of weekly nab-paclitaxel in combination with gemcitabine or carboplatin to the combination of gemcitabine and carboplatin as first line therapy in female subjects with Estrogen Receptor (ER), Progesterone Receptor (PgR), and human epidermal growth factor receptor 2 (HER2) negative (triple negative) metastatic breast cancer (TNMBC) or metastatic triple negative breast cancer. In the phase 2 portion of the study, the combinations of nab-paclitaxel plus gemcitabine and nab-paclitaxel plus carboplatin will be evaluated, and a comparator arm of gemcitabine combined with carboplatin will be used. In the phase 3 portion of the study, the selected nab-paclitaxel combination treatment will be compared to gemcitabine combined with carboplatin to evaluate progression free survival, safety and tolerability, overall survival, disease control rate and duration of response in women with metastatic triple negative breast cancer. Due to changes in the treatment landscape since the initiation of this trial, the decision was made not to proceed to the Phase 3 portion of the study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A subject will be eligible for inclusion in this study only if all of the following criteria are met:
- •Female subjects, age ≥ 18 years at the time informed consent is signed
- •Pathologically confirmed adenocarcinoma of the breast
- •Pathologically confirmed as triple negative, source documented, defined as both of the following
- •Estrogen Receptor (ER) and Progesterone Receptor (PgR) negative: \< 1% of tumor cell nuclei are immunoreactive in the presence of evidence that the sample can express ER or PgR (positive intrinsic controls)
- •Human Epidermal Growth Factor Receptor 2 (HER2) negative as per American Society of Clinical Oncology - College of American Pathologists (ASCO/CAP) guidelines i. Immunohistochemistry (IHC) 0 or 1 Fluorescence In Situ Hybridization (FISH) negative (or equivalent negative test). Subjects with IHC 2 must have a negative by Fluorescence In Situ Hybridization (FISH),, (or equivalent negative test).
- •Subjects with prior breast cancer history of different phenotypes (ie, ER/PgR/HER2 positive) must have pathologic confirmation of triple negative disease in at least one of the current sites of metastasis
- •Subjects must have received prior adjuvant or neoadjuvant anthracycline therapy; unless (a) anthracycline treatment was not indicated or was not the best treatment option for the subject in the opinion of the treating physician; and (b) anthracycline treatment remains not indicated or, in the opinion of the treating physician, is not the best treatment option for the subject's metastatic disease.
- •a. Newly diagnosed subjects presenting with TNMBC are eligible for the study if anthracycline treatment is not indicated or is not the best treatment option for the subject in the opinion of the treating physician.
- •Subjects with measurable metastatic disease, defined by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) guidelines
Exclusion Criteria
- •A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- •Male subjects
- •Concurrent chemotherapy or any other anti tumor therapy for breast cancer. Prior immunotherapy \& monoclonal antibody therapy are acceptable.
- •Subjects who received prior cytotoxic chemotherapy after incomplete resection of locoregional recurrent disease
- •History of, or known current evidence of brain metastasis, including leptomeningeal involvement.
- •Subjects with bone as the only site of metastatic disease
- •Subjects with regional lymph node as the only site of metastatic disease
- •Serious intercurrent medical or psychiatric illness, including serious active infection
- •History of class II-IV congestive heart failure or myocardial infarction within 6 months of randomization
- •History of other primary malignancy in the last 5 years prior to randomization. Subjects with prior breast cancer history are eligible, however, the most recently obtained biopsy must demonstrate triple negative disease (source documented). Subjects with prior history of in situ cancer or basal or localized squamous cell skin cancer are eligible.
Arms & Interventions
nab-Paclitaxel plus Gemcitabine
Treatment Arm A: nab-Paclitaxel 125 mg/m\^2 by intravenous (IV) administration over 30 minutes, followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 of each 21-day cycle by IV administration over 30 minutes
Intervention: nab-Paclitaxel
nab-Paclitaxel plus Gemcitabine
Treatment Arm A: nab-Paclitaxel 125 mg/m\^2 by intravenous (IV) administration over 30 minutes, followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 of each 21-day cycle by IV administration over 30 minutes
Intervention: Gemcitabine
nab-Paclitaxel plus Carboplatin
Treatment Arm B: nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin at an Area Under the Curve (AUC) of 2 on Days 1 and 8 of each 21-day cycle by IV administration
Intervention: nab-Paclitaxel
nab-Paclitaxel plus Carboplatin
Treatment Arm B: nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin at an Area Under the Curve (AUC) of 2 on Days 1 and 8 of each 21-day cycle by IV administration
Intervention: Carboplatin
Gemcitabine plus Carboplatin
Treatment Arm C: Gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin AUC 2 on Days 1 and 8 of each 21-day cycle by IV administration
Intervention: Carboplatin
Gemcitabine plus Carboplatin
Treatment Arm C: Gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin AUC 2 on Days 1 and 8 of each 21-day cycle by IV administration
Intervention: Gemcitabine
Outcomes
Primary Outcomes
Kaplan-Meier Estimates of Progression-Free Survival (PFS) Based on Investigator Assessment.
Time Frame: From date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C
PFS was defined as the time from the date of randomization to the date of disease progression or death from any cause on or prior to the data cutoff date for the statistical analysis, whichever occurred earlier. Tumor responses were assessed every 6 weeks using, Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and defined as: Complete response (CR) is the disappearance of all target lesions; Partial response (PR) occurs when at least a 30% decrease in the sum of diameters of target lesions from baseline; Stable disease is neither sufficient shrinkage to qualify for a PR nor sufficient increase of lesions to qualify for Progressive disease (PD); Progressive Disease- is at least a 20% increase in the sum of diameters of target lesions from nadir.
Secondary Outcomes
- Percentage of Participants Who Initiated Cycle 6 Receiving Doublet Combination Therapy(Cycle 6)
- Percentage of Participants With an Objective Complete or Partial Overall Response by Investigator Assessment.(Disease response was assessed every 6 weeks; from date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C)
- Kaplan-Meier Estimates of Overall Survival(From date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From randomization through to 28 days after the last dose of IP; up to data cut off date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C)
- Percentage of Participants Experiencing Dose Modifications (Reductions and Interruptions)(From randomization through to 28 days after the last dose of IP; up to data-cut off of date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C)
- Percentage of Participants Who Discontinued From All Study Treatment Due to TEAEs(From randomization through to 28 days after the last dose of IP; up to data-cut off of date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C)