Platinum for Triple-Negative Metastatic Breast Cancer and Evaluation of p63/p73 as a Biomarker of Response

NCT ID: NCT00483223

Last Updated: 2017-08-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30
• Study Completion Date: 2017-06-30

Brief Summary

The purpose of this research study is to :

• Determine how effective cisplatin or carboplatin is in slowing the time it takes for ER negative (estrogen-receptor-negative), PR negative (progesterone receptor-negative), HER2 negative (human epidermal growth factor receptor 2) breast cancer to progress. Cisplatin and carboplatin are anti-cancer chemotherapy drugs that stop cancer cells from growing abnormally and is used to treat other cancers.
• Evaluate a new biomarker to help determine which breast cancers are most likely to respond to cisplatin chemotherapy

The hypothesis is that Triple Negative metastatic breast cancer may be particularly sensitive to platinum, and that a subgroup of those patients may have a marker in their tumors that predicts response.

Detailed Description

This study is a Phase 2 study designed to evaluate cisplatin/carboplatin as first or second line therapy in metastatic triple negative (ER negative, PR negative, Her2 Negative) breast cancer and to evaluate the expression of p63/p73 as a biomarker to predict response.

• Participants will be given a cisplatin or carboplatin infusion intravenously on the first day of each treatment cycle. Each treatment cycle will last 3 weeks. Treating physician will select agent up to 41 patients in each cohort. Final primary endpoint analysis will use combined cis/carbo results.
• During all treatment cycles participants will have a physical exam (including weight and vital signs) and they will be asked general questions about their health and any medications they may be taking, as well as specific questions about any side effects they may be experiencing while receiving study treatment.
• During every treatment cycle participants will have standard blood tests to check blood counts, liver and kidney function, and a blood marker for you particular type of cancer.
• CT scans will be taken of the participants tumor every 2 to 3 cycles to assess the response of the tumor to cisplatin.
• Participants will be in this study for as long as they tolerate the study treatment and their disease does not get any worse.
• Participants will be required to have a sample of their original tumor sent to Massachusetts General Hospital for correlative studies, or a sample from a metastatic diagnostic biopsy.
• Patients with accessible tumor will be asked to provide an optional metastatic tumor biopsy for correlative studies.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm

Cisplatin or carboplatin (1 arm, 2 cohorts)

Group Type: EXPERIMENTAL

Cisplatin

Intervention Type: DRUG

Given intravenously on the first day of each 3-week treatment cycle at 75mg/m2. Participants may continue to receive study treatment as long as their disease does not worsen and they do not experience serious side effects.

carboplatin

Intervention Type: DRUG

Given intravenously on the first day of each 3-week treatment cycle at AUC 6. Participants may continue to receive study treatment as long as their disease does not worsen and they do not experience serious side effects.

Interventions

Cisplatin

Given intravenously on the first day of each 3-week treatment cycle at 75mg/m2. Participants may continue to receive study treatment as long as their disease does not worsen and they do not experience serious side effects.

Intervention Type: DRUG

carboplatin

Given intravenously on the first day of each 3-week treatment cycle at AUC 6. Participants may continue to receive study treatment as long as their disease does not worsen and they do not experience serious side effects.

Intervention Type: DRUG

Other Intervention Names

Platinol; Paraplatin

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed invasive breast cancer with stage IV disease, according to AJCC 6th edition (American Joint Committee on Cancer), either biopsy proven or with unequivocal evidence of metastatic disease by physical examination or radiological study
• All tumors must be ER-, PGR- and HER2-negative
• 18 years of age or older
• Paraffin tissue block is required from the primary tumor tissue or from diagnostic metastatic biopsy at time of relapse
• Measurable disease by RECIST
• Performance status of 0,1 or 2 by ECOG criteria (Eastern Cooperative Oncology Group)
• Life expectancy greater than 12 weeks
• Normal organ and bone marrow function documented within 14 days prior to enrollment as defined by the protocol

Exclusion Criteria

• More than 1 prior chemotherapy for the treatment of recurrent or metastatic breast cancer
• Prior treatment with cisplatin, carboplatin, or other platinum chemotherapy agents
• Active brain metastases or unevaluated neurological symptoms suggestive of brain metastases
• Intercurrent illness or other major medical condition or comorbid condition that might affect study participation
• Significant history of uncontrolled cardiac disease such as uncontrolled hypertension, unstable angina, recent myocardial infarction, uncontrolled congestive heart failure, cardiomyopathy either symptomatic or asymptomatic but with decreased ejection fraction <45%
• Renal dysfunction for which cisplatin dose would either require dose modification or would be considered unsafe
• Pregnant or nursing women
• History or other malignancy that was not treated with curative intent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: collaborator

North Shore Medical Center

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Steven Isakoff, MD, PhD

Attending Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steven Isakoff, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

University of Alabama-Birmingham

Birmingham, Alabama, United States

UCSF

San Francisco, California, United States

Georgetown - Lombardi Cancer Center

Washington D.C., District of Columbia, United States

Johns Hopkins University Medical Center

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

North Shore Medical Center

Peabody, Massachusetts, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Countries

United States

References

Isakoff SJ, Mayer EL, He L, Traina TA, Carey LA, Krag KJ, Rugo HS, Liu MC, Stearns V, Come SE, Timms KM, Hartman AR, Borger DR, Finkelstein DM, Garber JE, Ryan PD, Winer EP, Goss PE, Ellisen LW. TBCRC009: A Multicenter Phase II Clinical Trial of Platinum Monotherapy With Biomarker Assessment in Metastatic Triple-Negative Breast Cancer. J Clin Oncol. 2015 Jun 10;33(17):1902-9. doi: 10.1200/JCO.2014.57.6660. Epub 2015 Apr 6.

Reference Type: BACKGROUND

PMID: 25847936 (View on PubMed)

Other Identifiers

TBCRC009

Identifier Type: OTHER

Identifier Source: secondary_id

06-412

Identifier Type: -

Identifier Source: org_study_id