PARP Inhibition for Triple Negative Breast Cancer (ER-/PR-/HER2-)With BRCA1/2 Mutations

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Clovis Oncology, Inc.
Information provided by (Responsible Party):
Hoosier Oncology Group
ClinicalTrials.gov Identifier:
NCT01074970
First received: February 23, 2010
Last updated: September 12, 2013
Last verified: September 2013
  Purpose

The purpose of this trial is to evaluate 2-year disease-free survival in this patient population treated with single agent cisplatin and patients treated with cisplatin in combination with Rucaparib following preoperative chemotherapy. Side effects and tolerability of this treatment in patients with residual disease following preoperative chemotherapy will also be observed and characterized.


Condition Intervention Phase
Breast Cancer
Drug: Cisplatin
Drug: Rucaparib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: PARP Inhibition After Preoperative Chemotherapy in Patients With Triple Negative Breast Cancer or ER/PR +, HER2 Negative With Known BRCA1/2 Mutations: Hoosier Oncology Group BRE09-146

Resource links provided by NLM:


Further study details as provided by Hoosier Oncology Group:

Primary Outcome Measures:
  • Two-year Disease Free Survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    To evaluate 2-year disease-free survival (DFS), in patients with confirmed TNBC or ER/PR + HER2-, known BRCA1/2 mutations treated with single agent cisplatin and patients treated with cisplatin in combination with Rucaparib following preoperative chemotherapy


Secondary Outcome Measures:
  • Side Effects and Tolerability [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    To characterize the side effects and tolerability of cisplatin and cisplatin plus Rucaparib in patients with residual disease following preoperative chemotherapy.

  • One-year Disease Free Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To evaluate 1-year DFS

  • Overall Survival [ Time Frame: 60 months ] [ Designated as safety issue: No ]
    To determine 5-year overall survival

  • Pharmacokinetic Data [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To collect limited pharmacokinetic data, in patients receiving study drug to compliment ongoing PK analyses in other trials with Rucaparib

  • Specimen Collection [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To collect peripheral blood lymphocytes, archived tumor specimens, and genomic DNA to explore potential correlates of PARP inhibition, recurrence and toxicity.


Estimated Enrollment: 135
Study Start Date: February 2010
Estimated Study Completion Date: May 2014
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A: Cisplatin Monotherapy
Cisplatin 75 mg/m2 IV infusion over 60 minutes, D1 every 21 days for 4 cycles
Drug: Cisplatin
Cisplatin 75 mg/m2 IV infusion over 60 minutes, D1 every 21 days for 4 cycles
Active Comparator: Arm B: Combination Therapy

Rucaparib 24mg C1,30mg C2-4, D1,2,3 every 21 days for 4 cycles

Cisplatin 75 mg/m2 IV infusion over 60 minutes, D1 every 21 days for 4 cycles

Drug: Rucaparib
Rucaparib 24mg C1,30mg C2-4, D1,2,3 every 21 days for 4 cycles
Drug: Cisplatin
Cisplatin 75 mg/m2 IV infusion over 60 minutes, D1 every 21 days for 4 cycles

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have histologically or cytologically confirmed triple negative (ER-/PR-/HER2-) invasive breast cancer, stage I-III at diagnosis (AJCC 6th edition) based on initial evaluation by clinical examination and/or breast imaging. NOTE: Patients with ER+ and/or PR+ may enroll ONLY if they are known carriers of a deleterious mutation in BRCA1 or BRCA2. Patients with HER2+ tumors may not enroll regardless of BRCA status.
  • Must have completed preoperative (neoadjuvant) chemotherapy. NOTE: Acceptable preoperative regimens include an anthracycline or a taxane, or both. Patients may NOT have received cisplatin as part of their neoadjuvant therapy regimen. Patients who received preoperative therapy as part of a clinical trial may enroll. No adjuvant chemotherapy after surgery other than that specified in this protocol is allowed. Adjuvant bisphosphonate use is allowed.
  • Must have completed definitive resection of primary tumor. The last surgery for breast cancer must have been completed at least 14 days prior to registration for protocol therapy.
  • Must have significant residual invasive disease at the time of definitive surgery following preoperative chemotherapy. Significant residual disease is defined at least one of the following:

    • Miller-Payne response in the breast of 0-25.
    • Residual Cancer Burden (RBC) classification II or III6
    • Residual carcinoma in one or more regional lymph nodes that would meet AJCC 6th edition criteria for N1 - N3 disease.
    • Alternatively, if Miller-Payne or RCB grading is not available, the patient will be eligible if the pathology report indicates that the area of residual invasive disease in the breast measures at least 2 cm following preoperative therapy. The presence of DCIS without invasion does not qualify as residual disease in the breast.
  • Whole breast radiotherapy is required for patients who underwent breast conserving therapy, including lumpectomy or partial mastectomy. Patients receiving adjuvant radiation therapy must have completed radiotherapy at least 14 days prior to registration for protocol therapy.
  • Written informed consent and HIPAA authorization for release of personal health information.
  • Age > 18 years at the time of consent.
  • Must consent to allow submission of archived tumor tissue sample from definitive surgery.
  • Must consent to collection of blood samples for PK analysis.
  • Women of childbearing potential and males must be willing to use an effective method of contraception from the time consent is signed until 4 weeks after treatment discontinuation.
  • Women of childbearing potential must have a negative pregnancy test within 14 days prior to registration for protocol therapy.
  • Women must not be breastfeeding.

Exclusion Criteria:

  • No stage IV (metastatic) disease, however no specific staging studies are required in the absence of symptoms or physical exam findings that would suggest distant disease.
  • No treatment with any investigational agent within 30 days prior to registration for protocol therapy.
  • No history of chronic hepatitis B or C
  • No clinically significant infections as judged by the treating investigator.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01074970

  Show 27 Study Locations
Sponsors and Collaborators
Hoosier Oncology Group
Clovis Oncology, Inc.
Investigators
Study Chair: Kathy D. Miller, M.D. Hoosier Oncology Group
  More Information

Additional Information:
No publications provided

Responsible Party: Hoosier Oncology Group
ClinicalTrials.gov Identifier: NCT01074970     History of Changes
Other Study ID Numbers: BRE09-146
Study First Received: February 23, 2010
Last Updated: September 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Hoosier Oncology Group:
PARP inhibition + breast cancer
breast cancer
PARP inhibitor
Triple negative

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 22, 2014