Clinical trial NCT00483223: Platinum for Triple-Negative Metastatic Breast Cancer and Evaluation of p63/p73 as a Biomarker of Response
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: ER negative
PgR negative
HER2 negative
cisplatin
carboplatinum
platinum
p63
p73
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Beth Israel Deaconess Medical Center
name: Dana-Farber Cancer Institute
name: North Shore Medical Center
First posted: 2007-06-06
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective Response Rate
timeFrame: 3 years
measure: Response Rate Categorized by p63/p73 Ratio
timeFrame: 3 years
Secondary outcomes:
measure: Objective Response Rate Categorized by Subgroup
timeFrame: 3 years
measure: Progression Free Survival and Overall Survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama-Birmingham
state: Alabama
city: San Francisco
country: United States
facility: UCSF
state: California
city: Washington, D.C.
country: United States
facility: Georgetown - Lombardi Cancer Center
state: District of Columbia
city: Baltimore
country: United States
facility: Johns Hopkins University Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Peabody
country: United States
facility: North Shore Medical Center
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
Study officials:
affiliation: Massachusetts General Hospital
name: Steven Isakoff, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.