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Expanded Access With ABT-888 (Veliparib) to Treat Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02985658
Expanded Access Status : Available
First Posted : December 7, 2016
Last Update Posted : November 12, 2018
Information provided by (Responsible Party):
University of Washington

Tracking Information
First Submitted Date December 5, 2016
First Posted Date December 7, 2016
Last Update Posted Date November 12, 2018
Descriptive Information
Brief Title Expanded Access With ABT-888 (Veliparib) to Treat Metastatic Breast Cancer
Brief Summary This is an expanded access protocol to allow continued maintenance therapy with ABT-888 (veliparib) for three patients with metastatic triple negative breast cancer who are currently receiving the investigational product in association with clinical trial participation. Additionally, the protocol will enroll up to 7 new patients with metastatic BRCA associated or triple negative breast cancer to allow for additional access to veliparib monotherapy, or at the investigator's discretion, veliparib in combination with cisplatin and/or vinorelbine.
Detailed Description

ABT-888 (Veliparib) or Poly(ADP-ribose)-polymerase (PARP) is a nuclear enzyme that recognizes deoxyribonucleic acid (DNA) damage and facilitates DNA repair. Inactive PARPs 1 and 2 bind to damaged DNA, which leads to their auto-activation. The resulting activated PARP then poly(ADP-ribosyl)ates many nuclear target proteins, including those that facilitate DNA repair of both single-stranded or double-stranded DNA breaks. Thus, PARP inhibition will result in less efficient DNA repair following a DNA damage insult.

Since cancer cells are genetically unstable, often exhibiting complex karyotypes that include large deletions, insertions, and unbalanced translocations of chromosomal fragment, these cells are more susceptible than normal tissues to cytotoxicity induced by DNA-damaging agents.Of these, deficiencies in mismatch repair and homologous recombination are associated with the largest number of malignancies, including many sporadic TNBCs. These deficiencies render cells more dependent on PARP for DNA repair and, hence, are more prone to cytotoxicity induced by PARP inhibition. In particular, tumor cells with BRCA1 or BRCA2 deficiencies are exquisitely sensitive to PARP inhibition, even in the absence of any other insults. Identification of sporadic TNBC with defects in homologous recombination and mismatch repair independent of germline mutation of BRCA 1 and 2 is an active area of research interest.

PARP-enabled DNA repair may also compensate for the loss of other repair pathways. Higher expression of PARP in cancer cells compared to normal cells has been linked to drug resistance and the overall ability of cancer cells to sustain genotoxic stress.

The combination of platinum based chemotherapy and PARP inhibition may be most effective in TNBC, and particularly in subsets of TNBC. This combination may also be active in tumors with a germline BRCA1-deficiency and/or basal phenotype, since a defect in the DNA double-strand break repair pathway should increase sensitivity to these agents. The addition of a PARP inhibitor to platinum based chemotherapy may induce a "double hit" to tumor cells lacking homologous recombination without causing excess toxicity to normal cells. ABT-888 may be used in combination with the DNA damaging agent, cisplatin, to potentiate its cytotoxic effect and with vinorelbine to enhance tumor response rate. Safety and preliminary efficacy of veliparib in combination with cisplatin and vinorelbine in patients with advanced triple negative and BRCA-associated breast cancer has been reported.

Study Type Expanded Access
  • Drug: Veliparib

    Patients will start veliparib at 300 mg po BID days 1 through 21 of the first 21 day cycle, then increase to 400 mg po BID days 1 through 21 of each subsequent cycle, as tolerated by the patient.

    At the treating investigator's discretion, and with principal investigator approval, veliparib may be used in combination with cisplatin and/or vinorelbine. Veliparib (300mg) will be dosed po BID on Days 1 through 14 of each 21-day cycle.

    The patient will receive therapy as long as there is therapeutic benefit

    Other Name: ABT-888
  • Drug: Cisplatin
    Cisplatin will be administered intravenously (75 mg/m2) on Day 1 of each cycle
    Other Names:
    • Platinol-AQ
    • Platinol
  • Drug: Vinorelbine
    Vinorelbine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle
    Other Name: Navelbine
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Expanded Access Status Available
Contact: Jennifer Specht, MD 206-606-6329
Listed Location Countries United States
Removed Location Countries  
Administrative Information
NCT Number NCT02985658
Responsible Party University of Washington
Study Sponsor University of Washington
Collaborators AbbVie
Investigators Not Provided
PRS Account University of Washington
Verification Date November 2018