|Phase II||Biomarker/Laboratory analysis, Treatment||Closed||18 and over||Other||BRE09-146|
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.
Further Study Information
OUTLINE: This is a multi-center study.
Safety Run-in will be for the first 12 patients on study only (6 in cohort 1 and 6 in cohort 2). Patients in the safety run will be included in the efficacy analysis on intent to treat basis:
Cisplatin 75 mg/m2 IV D1 every 3 weeks x 4 cycles; Rucaparib 16-30 mg IV D 1,2,3 every 3 weeks x 4 cycles
If cycle 1 is well tolerated, the dose of Rucaparib will be escalated from 16 mg to 24 mg for subsequent cycles in the cohort 1, and 24 mg to 30 mg in the cohort 2.
If ≤ 1 of 6 patients in cohort 1 experiences DLT, cohort 2 will commence. If 2 or more of 6 patients in cohort 1 experience DLT, the study will be suspended and an amendment to explore lower doses will be considered.
If ≤ 1 of 6 patients in cohort 2 experiences DLT, the randomized portion of the study will commence. If 2 or more of 6 patients experience DLT, the study will be suspended and an amendment to proceed with the randomized portion at the cohort 2 dose (24 mg) will be considered.
During the randomized portion of the study, patients will be randomized to either Arm A or Arm B.
- Anthracycline vs. not
- Residual LN involvement vs. No Residual LN involvement
Arm A (Cisplatin Monotherapy) Cisplatin 75 mg/m2 IV D1 every 3 weeks x 4 cycles
Arm B (Combination Therapy) Cisplatin 75 mg/m2 IV D1 every 3 weeks x 4 cycles; Rucaparib 16-30 mg IV D1,2,3 every 3 weeks x 4 cycles
Rucaparib maintenance 30 mg IV weekly x 24 weeks
ECOG Performance Status 0-1
Life Expectancy: Not Specified
- Hemoglobin (Hgb) > 9.0 g/dL
- Platelets > 100 K/ mm3
- Absolute neutrophil count (ANC) > 1.5 K/mm3
- Bilirubin < upper limit of normal (except in patients with documented Gilbert's disease, who must have a total bilirubin < 3.0 mg/dL)
- Aspartate aminotransferase (AST, SGOT) < 2.5 x ULN
- Alanine aminotransferase (ALT, SGPT) < 2.5 x ULN
- Calculated creatinine clearance of > 50 cc/min using the Cockcroft-Gault formula
- Left ventricular ejection fraction within normal limits.
- Patients with an unstable angina or myocardial infarction within 12 months of study entry are excluded.
- No clinically significant arrhythmia or baseline ECG abnormalities in the opinion of the treating investigator.
- 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.
- 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.
Trial Lead Organizations/Sponsors
Hoosier Oncology Group, IncorporatedClovis Oncology
|Kathy Miller||Study Chair|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01074970
ClinicalTrials.gov processed this data on October 17, 2013
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