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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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Breast Cancer

Thank you

Trial Information

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


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.

Stratification factors:

- 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

Hematopoietic:

- Hemoglobin (Hgb) > 9.0 g/dL

- Platelets > 100 K/ mm3

- Absolute neutrophil count (ANC) > 1.5 K/mm3

Hepatic:

- 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

Renal:

- Calculated creatinine clearance of > 50 cc/min using the Cockcroft-Gault formula

Cardiovascular:

- 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.


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.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Two-year Disease Free Survival

Outcome Description:

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

Outcome Time Frame:

24 months

Safety Issue:

No

Principal Investigator

Kathy D. Miller, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

Hoosier Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

BRE09-146

NCT ID:

NCT01074970

Start Date:

February 2010

Completion Date:

May 2014

Related Keywords:

  • Breast Cancer
  • PARP inhibition + breast cancer
  • breast cancer
  • PARP inhibitor
  • Triple negative
  • Breast Neoplasms

Name

Location

University of Colorado Cancer CenterDenver, Colorado  80262
Virginia Oncology AssociatesNewport News, Virginia  23606
Comprehensive Cancer Centers of NevadaLas Vegas, Nevada  89109
Indiana University Melvin and Bren Simon Cancer CenterIndianapolis, Indiana  46202-5289
Hope A Women's Cancer CenterAsheville, North Carolina  28801
Siteman Cancer CenterSaint Louis, Missouri  63110
University of California Los AngelesLos Angeles, California  90095-6951
Oregon Health Sciences UniversityPortland, Oregon  
The West ClinicMemphis, Tennessee  38120
Northern Indiana Cancer Research ConsortiumSouth Bend, Indiana  
The Center for Cancer & Hematologic DiseaseCherry Hill, New Jersey  08003
Central Coast Medical Oncology CorporationSanta Maria, California  93454
Community Regional Cancer CenterIndianapolis, Indiana  46256
Fort Wayne Oncology & Hematology, IncFort Wayne, Indiana  46815
University of Miami, Sylvester Comprehensive Cancer CenterMiami, Florida  33136
Presbyterian Medical GroupAlbuquerque, New Mexico  87110
St. Jude Heritage HealthcareFullerton, California  92835
Monroe Medical AssociatesMunster, Indiana  46321
Metro Health Cancer CareWyoming, Michigan  49519
University of New Mexico Cancer Care AllianceAlbuquerque, New Mexico  87131
Memorial Cancer Institute Breast Cancer CenterHollywood, Florida  33021
Horizon Oncology Research, Inc./IU Health ArnettLafayette, Indiana  47905
Virtua Health Cancer ProgramMount Holly, New Jersey  08060
South Jersey Health CareVineland, New Jersey  08360
Seidman Cancer CenterCleveland, Ohio  44106
Pinnacle Health Fox Chase Regional Cancer CenterHarrisburg, Pennsylvania  17110
Bux-Mont Oncology Hematology Associates (FCCC) at Grand View HospitalSellersville, Pennsylvania  18960