A Study of (a) Veliparib and Temozolomide or (b) Veliparib, Carboplatin and Paclitaxel or (c) Placebo, Carboplatin and Paclitaxel in patients with Breast Cancer

Phase 1

Conditions: BRCA1 or BRCA2 mutation metastatic breast cancer
MedDRA version: 17.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2011-002913-12-CZ

Lead Sponsor: AbbVie Deutschland GmbH & Co. KG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 255

Inclusion Criteria

Histologically or cytologically confirmed breast cancer with evidence of metastatic disease.
Must have a documented deleterious BRCA1 or BRCA2 germline mutation. The investigator should ensure that the testing is consistent with local guidelines, and clinical practice, and that the test uses either 1) direct DNA sequencing/multiplex ligation-dependent probe amplification (MLPA) or 2) a well-characterized methodology previously validated by sequencing, such as that used to assess founder mutations. If testing has been performed by a laboratory other than Sponsor core laboratory, subjects may be enrolled and must be re-tested by Sponsor core laboratory for confirmation of BRCA1 or BRCA2 germline mutations.
If HER2 positive (HER2 3+ by immunohistochemistry or amplification by fluorescence in situ hybridization [FISH > 2]), subjects must have received and progressed on at least one prior standard HER2-directed therapy or the subject must be ineligible to receive anti-HER2 therapy. Measurable lesion by RECIST (version 1.1) on computed tomography (CT) scan (within 21 days of C1D1) in at least one site. If only a single measurable lesion exists, it cannot be a bone or cystic lesion. Bone-only, lymphangitic pulmonary metastases, and previously irradiated tumors will be considered nonmeasurable.
ECOG Performance status of 0 to 2.
Adequate hematologic, renal, and hepatic function
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 245
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

Received anticancer agent(s), an investigational agent, or radiotherapy within 28days or 5 half lives; whichever is shorter, prior to C1D1. Prior treatment with palliative local breast or bone lesion radiation (other than pelvis) can occur within 14 days of C1D1. Subjects experiencing a significant adverse effect or toxicity (Grade 3 or Grade 4), causally attributed to previous anticancer treatment that has not recovered to at least Grade 2 are excluded. Anticancer hormonal therapy must be stopped 7 days prior to C1D1. Subjects receiving bisphosphonates are eligible.
More than 1 prior line of cytotoxic chemotherapy (e.g., gemcitabine, doxorubicin, capecitabine) for metastatic disease. Regimens received in the adjuvant/neoadjuvant setting within the past 6 months will also be considered toward the maximum of 1 prior line of therapy. In order to count as a line of therapy, a cytotoxic agent must have been administered for at least 1 full cycle. Previous treatments with hormonal therapy (tamoxifen, aromatase inhibitors) and signal transduction agents (e.g., trastuzumab lapatinib, erlotinib, gefitinib, bevacizumab) are allowed and are not counted towards the prior line of therapy.
Prior therapy with temozolomide, a platinum agent, or a Poly-(ADP-ribose)-Polymerase (PARP) inhibitor.
Prior taxane therapy for metastatic disease. Use of taxanes as adjuvant therapy is permitted, if given more than 6 months prior to C1D1.
A history of or evidence of brain metastases or leptomeningeal disease. Subjects with symptoms to suggest central nervous system (CNS) metastases should have a brain MRI within 21 days of enrollment to confirm the absence of CNS metastases. Contrast CT is acceptable for subjects who are unable to undergo a brain MRI.
A history of uncontrolled seizure disorder.
Pre-existing neuropathy from any cause in excess of Grade 1.
Known history of allergic reactions to cremophor-paclitaxel.
Clinically significant uncontrolled condition(s).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the progression-free survival of oral veliparib in combination with temozolomide or in combination with carboplatin and paclitaxel compared to placebo plus carboplatin and paclitaxel in subjects with BRCA1 or BRCA2 mutation and<br>metastatic breast cancer.;Secondary Objective: To assess overall survival, clinical benefit rate & objective response rate in those subjects treated with veliparib plus TMZ or treated with veliparib plus carboplatin and paclitaxel versus placebo plus carboplatin and paclitaxel.;Primary end point(s): Progression Free Survival;Timepoint(s) of evaluation of this end point: Progression Free Survival is defined as the number of days from the date the subject was randomized to the date the subject experienced a confirmed event of disease progression (as determined by the central imaging center), or to the date of death (all causes of mortality), if disease progression is not reached.

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: Overall Survival - number of days from randomization to date of death<br>Clinical Benefit Rate - number of subjects with at least 1 stable disease through end of Week 18 based on central imaging read.<br>Objective Response Rate - subjects who have a partial or complete response based on assessment by central imaging read.;Secondary end point(s): Overall Survival, Clinical Benefit Rate and Objective Response Rate

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