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

Phase 2

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Cisplatin; Drug: carboplatin

• Registration Number: NCT00483223
• Lead Sponsor: Massachusetts General Hospital

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.

Study Timeline

• Study Start: 2007-06
• Study First Submitted: 2007-06-05
• Study First Submitted QC: 2007-06-05
• Study First Posted: 2007-06-06
• Primary Completion: 2014-06
• Results First Submitted: 2017-04-13
• Results First Submitted QC: 2017-05-25
• Study Completion: 2017-06
• Results First Posted: 2017-06-01
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-25
• Last Update Posted: 2017-08-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 86

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single Arm	Cisplatin	Cisplatin or carboplatin (1 arm, 2 cohorts)
Single Arm	carboplatin	Cisplatin or carboplatin (1 arm, 2 cohorts)

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	3 years	Objective response rate (ORR) (complete response \[CR\]+ partial response \[PR\]) by RECIST (Response Evaluation Criteria In Solid Tumors).; Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the LD (longest diameter) of target lesions, taking as reference the baseline sum LD; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Response Rate Categorized by p63/p73 Ratio	3 years	Response rate categorized by pre-specified ΔNp63/TAp73 expression ratio cutoff in the primary tumors from this patient cohort as a bio-marker to predict response to cisplatin or carboplatin. Response is defined as partial or completed response as determined by RECIST. Expression ratio was measured using quantitative RT-PCR (Reverse transcription polymerase chain reaction).

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate Categorized by Subgroup	3 years	The number of participants achieving an objective response (as determined by RECIST) categorized by treatment cohort and whether the treatment was first or second line treatment. First line treatment means that the drug used was the first drug used for the treatment of the primary cancer. Second line treatment means that a first line treatment failed to produce the desired response, so a new drug was used for treatment.
Progression Free Survival and Overall Survival	5 years	Median progression free survival and overall survival (progression determined using RECIST) during a median follow-up time of 50 months.

Trial Locations

Locations (10)

University of Alabama-Birmingham; 🇺🇸 Birmingham, Alabama, United States

UCSF; 🇺🇸 San Francisco, California, 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

Georgetown - Lombardi Cancer Center; 🇺🇸 Washington, D.C., District of Columbia, 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