Research Study Summary
A Randomized Phase 2 Study of the Efficacy and Tolerability of Veliparib in Combination with Temozolomide or Veliparib in Combination with Carboplatin and Paclitaxel Versus Placebo Plus Carboplatin and Paclitaxel in Subjects with BRCA1 or BRCA2 Mutation and Metastatic Breast Cancer
Patient Inclusion Criteria:
Subjects will be adult men and women with metastatic breast cancer and a documented deleterious BRCA1 or BRCA2 germline mutation.
Subjects must meet all of the following inclusion criteria to be eligible:
- = 18 years of age.
- 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
- direct DNA sequencing/MLPA or
- 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 the Sponsor core laboratory, subjects may be enrolled but 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 FISH
> 2), subjects must have progressed on at least one prior standard HER2 directed therapy or have a contraindication to anti-HER2 therapy.
- . Measurable lesion by RECIST (version 1.1) on CT scan (within 21 days of C1D1) in at least one site that has not received prior radiotherapy, unless progression has been demonstrated in the lesion. If only a single measurable lesion exists, it can not be a bone or cystic lesion (refer to Section 188.8.131.52). Bone-only lymphangitic pulmonary metastases and previously irradiated tumors without subsequent progression will be considered non-measurable.
- ECOG performance status of 0 to 2 (within 28 days of C1D1).
- Adequate hematologic, renal, and hepatic function as follows (within 28 days of C1D1):
- Bone Marrow: Absolute neutrophil count (ANC) = 1500/mm3 (1.5 × 109/L);
Platelets = 100,000/mm3 (100 × 109/L); Hemoglobin = 9.5 g/dL (1.4 mmol/L);
Leukocytes > 3,000/mm3;
- Renal Function: Serum creatinine = 1.5 × upper limit of normal (ULN) range OR creatinine clearance = 50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal;
- Hepatic Function: AST and/or ALT = 2.5 × institutional upper limit of
normal. For subjects with liver metastases, AST and/or ALT < 5 × ULN
range; bilirubin = 1.5 × the ULN range. Subjects with Gilbert's syndrome may have a bilirubin = 1.5 × the ULN range, if no evidence of biliary obstruction exists;
- Activated Partial Thromboplastin Time (APTT) must be = 1.5 × the ULN range and INR < 1.5. Subjects on anticoagulant therapy will have an appropriate PTT and INR as determined by the investigator.
- Women of childbearing potential and men must agree to use adequate contraception (one of the following listed below) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to initiation of treatment. To be considered of non-child bearing potential, postmenopausal women must be amenorrheic for at least 12 months or subjects must be surgically sterile.
- Total abstinence from sexual intercourse (for minimum of one complete menstrual cycle prior to study drug administration);
- Vasectomized male subjects or vasectomized partner of female subjects;
- Double-barrier method (condoms, contraceptive sponge, diaphragm, or vaginal
ring with spermicidal jellies or cream); or
- Intra-Uterine Device (IUD).
- Additionally, male subjects (including those who are vasectomized) whose
partners are pregnant or might be pregnant must agree to use condoms for the duration of the study and for 90 days following completion of therapy.
- Capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by an IEC/IRB, prior to initiation of any screening or study-specific procedures.
Patient Exclusion Criteria:
Subjects must meet none of the following exclusion criteria to be eligible.
- . Received anticancer agent(s), an investigational agent or radiotherapy, within
28 days 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, if administered at least 14 days prior to C1D1. Subjects experiencing a significant
adverse effect or toxicity (Grade 3 or 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 before starting 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
towards 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 toward the prior line of therapy.
- Prior therapy with temozolomide, a platinum agent, or a 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 suggestive of 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 reaction to cremophor/paclitaxel.
- Clinically significant uncontrolled condition(s) including, but not limited to:
- Active infection;
- Symptomatic congestive heart failure;
- Unstable angina pectoris or cardiac arrhythmia;
- Myocardial infarction within last 6 months;
- Psychiatric illness/social situations that would limit compliance with study
- Any medical condition that, in the opinion of the investigator, places the subject at an unacceptably high risk for toxicities.
- A previous or concurrent cancer that is distinct in primary site or histology from metastatic breast cancer, except cervical carcinoma in situ, non-melanoma
carcinoma of the skin, or in situ carcinoma of the bladder. Any cancer curatively
treated more than 3 years prior to entry is permitted. For these subjects, metastases must be histologically or cytologically confirmed to be breast cancer.
- Pregnant or breastfeeding.
To Learn more
CW ID: 180068
Date Last Changed:
July 19, 2013
Clinical Trial Snapshot
- Both Male and Female
- 18 and up
- Overall Status
- Facility Type
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