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

Sponsor:	Massachusetts General Hospital
Collaborators:	Beth Israel Deaconess Medical Center Dana-Farber Cancer Institute North Shore Medical Center
Information provided by (Responsible Party):	Steven Isakoff, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00483223

Purpose

The purpose of this research study is to :

Determine how effective cisplatin or carboplatin is in slowing the time it takes for ER negative, PR negative, HER2 negative 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.

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

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Study of Cisplatin or Carboplatin for Triple-Negative Metastatic Breast Cancer and Evaluation of p63/p73 as a Biomarker of Response

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Cisplatin Carboplatin

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

To determine the objective response rate in patients with ER/PgR/HER2 negative metastatic breast cancer receiving platinum as first or second-line therapy. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
To evaluate the expression of p63/p73 in primary tumors from this patient cohort as a biomarker to predict response to platinum [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the progression free survival, clinical benefit rate, and overall survival in patients with triple-negative metastatic breast cancer receiving first line platinum therapy [ Time Frame: TBD ] [ Designated as safety issue: No ]
To evaluate the safety and toxicity of platinum therapy in this patient population. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
To conduct correlative studies to learn more about the biology of triple negative breast cancer. [ Time Frame: TBD ] [ Designated as safety issue: No ]

Estimated Enrollment:	82
Study Start Date:	June 2007
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	November 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Single Arm Cisplatin or carboplatin (1 arm, 2 cohorts)	Drug: 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. Other Name: Platinol Drug: carboplatin Given intravenously on the first day of each 3-week treatment cycle at AUC6. Participants may continue to receive study treatment as long as their disease does not worsen and they do not experience serious side effects.

Arms

Assigned Interventions

Experimental: Single Arm

Cisplatin or carboplatin (1 arm, 2 cohorts)

Drug: 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.

Other Name: Platinol

Drug: carboplatin

Given intravenously on the first day of each 3-week treatment cycle at AUC6. Participants may continue to receive study treatment as long as their disease does not worsen and they do not experience serious side effects.

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.

Eligibility

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

Criteria

Inclusion Criteria:

Histologically confirmed invasive breast cancer with stage IV disease, according to AJCC 6th edition, 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
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00483223

Locations

United States, Alabama
University of Alabama-Birmingham
Birmingham, Alabama, United States
United States, California
UCSF
San Francisco, California, United States
United States, District of Columbia
Georgetown - Lombardi Cancer Center
Washington, District of Columbia, United States
United States, Maryland
Johns Hopkins University Medical Center
Baltimore, Maryland, United States
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
North Shore Medical Center
Peabody, Massachusetts, United States, 01960
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States

Sponsors and Collaborators

Massachusetts General Hospital

Beth Israel Deaconess Medical Center

Dana-Farber Cancer Institute

North Shore Medical Center

Investigators

Principal Investigator:

Steven Isakoff, MD, PhD

Massachusetts General Hospital

More Information

Additional Information:

Mass General Hospital Cancer Center - Breast Oncology Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Steven Isakoff, MD, PhD, Attending Physician, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00483223 History of Changes
Other Study ID Numbers:	06-412, TBCRC009
Study First Received:	June 5, 2007
Last Updated:	April 9, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:

ER negative
PgR negative
HER2 negative
cisplatin

carboplatinum
platinum
p63
p73

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cisplatin

Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 22, 2012