Description:
The study seeks to evaluate the efficacy and tolerability of veliparib/placebo in combination
with carboplatin and paclitaxel in HER2-negative metastatic or locally advanced,
unresectable, BRCA-associated breast cancer.
Title
- Brief Title: A Phase 3 Randomized, Placebo-controlled Trial of Carboplatin and Paclitaxel With or Without Veliparib (ABT-888) in HER2-negative Metastatic or Locally Advanced Unresectable BRCA-associated Breast Cancer
- Official Title: A Phase 3 Randomized, Placebo-Controlled Trial of Carboplatin and Paclitaxel With or Without the PARP Inhibitor Veliparib (ABT-888) in HER2 Negative Metastatic or Locally Advanced Unresectable BRCA-Associated Breast Cancer
Clinical Trial IDs
- ORG STUDY ID:
M12-914
- SECONDARY ID:
2014-000345-70
- NCT ID:
NCT02163694
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Paclitaxel | Taxol | Veliparib Placebo with Carboplatin and Paclitaxel |
Veliparib | ABT-888 | Veliparib with Carboplatin and Paclitaxel |
Carboplatin | | Veliparib Placebo with Carboplatin and Paclitaxel |
Veliparib Placebo | | Veliparib Placebo with Carboplatin and Paclitaxel |
Purpose
The study seeks to evaluate the efficacy and tolerability of veliparib/placebo in combination
with carboplatin and paclitaxel in HER2-negative metastatic or locally advanced,
unresectable, BRCA-associated breast cancer.
Trial Arms
Name | Type | Description | Interventions |
---|
Veliparib Placebo with Carboplatin and Paclitaxel | Active Comparator | Veliparib Placebo on Day -2 through 5 of a 21-day cycle. Carboplatin on Day 1 of a 21-day cycle and paclitaxel on Day 1, 8, and 15 of a 21-day cycle. | - Paclitaxel
- Carboplatin
- Veliparib Placebo
|
Veliparib with Carboplatin and Paclitaxel | Experimental | Veliparib on Day -2 through 5 of a 21-day cycle. Carboplatin on Day 1 of a 21-day cycle and paclitaxel on Day 1, 8, and 15 of a 21-day cycle. | - Paclitaxel
- Veliparib
- Carboplatin
|
Eligibility Criteria
Inclusion Criteria:
1. Histologically or cytologically confirmed breast cancer that is either locally
advanced or metastatic. Locally advanced breast cancer must not be amenable to
surgical resection or radiation with curative intent.
2. Suspected deleterious or deleterious BRCA1 and/or BRCA2 germline mutation.
3. Breast cancer must be HER2-negative.
4. Measurable or non-measurable (but radiologically evaluable) disease per Response
Evaluation Criteria In Solid Tumors (RECIST), version 1.1 on computed tomography (CT)
scan (within 28 days of randomization) with at least one lesion outside previously
irradiated areas.
5. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2.
6. Adequate hematologic, renal, and hepatic function (within 28 days of randomization).
Exclusion Criteria:
1. More than two prior lines of cytotoxic chemotherapy (e.g., gemcitabine, doxorubicin,
capecitabine) for metastatic disease.
- Regimens received in the adjuvant/neoadjuvant setting or for locally advanced
breast cancer within the past 6 months will also be considered toward the maximum
of 2 prior lines of therapy. Adjuvant/neoadjuvant chemotherapy for one cancer
event will count as one prior line of therapy, if received within the past 6
months.
- Previous treatments with hormonal therapy (tamoxifen, aromatase inhibitors) and
signal transduction agents (e.g., erlotinib, gefitinib, everolimus, bevacizumab)
are allowed and are not counted towards the prior line of therapy.
2. Progressed or recurred within 12 months of completing platinum therapy or received > 1
prior line of platinum therapy for breast cancer in any setting (adjuvant,
neoadjuvant, or metastatic).
3. Prior therapy with PARP inhibitors.
4. Prior taxane therapy administered for the treatment of metastatic breast cancer with
the below exceptions.
- Prior taxane therapy for metastatic breast cancer is allowed if the patient
received ≤ 1 full cycle (i.e., therapy discontinued within 4 weeks for subjects
receiving weekly paclitaxel or Abraxane; therapy discontinued within 3 weeks for
subjects receiving paclitaxel or docetaxel every 3 weeks) in the absence of
progression or if taxane therapy for metastatic disease was > 12 months prior to
C1D-2.
- Use of taxanes as adjuvant therapy or to treat locally advanced disease is
permitted, if given more than 6 months prior to C1D-2
5. Known history of allergic reaction to cremophor-paclitaxel, carboplatin, Azo-Colourant
Tartrazine (also known as FD&C Yellow 5 or E102), Azo-Colourant Orange Yellow-S (also
known as FD&C Yellow 6 or E110) or known contraindications to any study supplied drug.
6. Active CNS metastases or leptomeningeal disease.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression free survival (PFS) |
Time Frame: | Measured up to 3 years after the last subject has enrolled in the study. |
Safety Issue: | |
Description: | Number of days from the date the subject is randomized to the date the subject experiences a confirmed event of disease progression or to the date of death if disease progression is not reached |
Secondary Outcome Measures
Measure: | Overall survival (OS) |
Time Frame: | Measured up to 5 years after the last subject has enrolled in the study. |
Safety Issue: | |
Description: | Number of days from the day the subject is randomized to the date of the subject's death |
Measure: | Clinical benefit rate (CBR) |
Time Frame: | Measured up to 5 years after the last subject has enrolled in the study. |
Safety Issue: | |
Description: | Progression-free rate at 24 weeks from the Kaplan-Meier curve for time to progression |
Measure: | Objective response rate (ORR) |
Time Frame: | Measured up to 2 years after the last subject has enrolled in the study. |
Safety Issue: | |
Description: | Proportion of subjects with a complete or partial objective response |
Measure: | Progression-free survival 2 (PFS2) |
Time Frame: | Measured up to 5 years after the last subject has enrolled in the study. |
Safety Issue: | |
Description: | Days from randomization to the second objective radiographic progression or death of any cause after the first objective radiographic progression, whichever occurs first |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | AbbVie |
Trial Keywords
- PARP Inhibitor
- Veliparib
- BRCA1
- BRCA2
- HER2-negative
- Locally recurrent
- Breast Cancer
- Metastatic Breast Cancer
- ABT-888
- Genetic breast cancer
- Paclitaxel
- BRCA Mutation
- PARP
- Carboplatin
- BROCADE3
Last Updated
August 10, 2021