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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00483223
First Posted: June 6, 2007
Last Update Posted: August 25, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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
June 5, 2007
June 6, 2007
April 13, 2017
June 1, 2017
August 25, 2017
June 2007
June 2014   (Final data collection date for primary outcome measure)
  • Objective Response Rate [ Time Frame: 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 [ Time Frame: 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).
  • To determine the objective response rate in patients with ER/PgR/HER2 negative metastatic breast cancer receiving cisplatin as first-line therapy.
  • To evaluate the expression of p63/p73 in primary tumors from this patient cohort as a biomarker to predict response to cisplatin
Complete list of historical versions of study NCT00483223 on ClinicalTrials.gov Archive Site
  • Objective Response Rate Categorized by Subgroup [ Time Frame: 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 [ Time Frame: 5 years ]
    Median progression free survival and overall survival (progression determined using RECIST) during a median follow-up time of 50 months.
  • To determine the progression free survival, clinical benefit rate, and overall survival in patients with triple-negative metastatic breast cancer receiving first line cisplatin therapy
  • To evaluate the safety and toxicity of cisplatin therapy in this patient population.
Not Provided
Not Provided
 
Platinum for Triple-Negative Metastatic Breast Cancer and Evaluation of p63/p73 as a Biomarker of Response
A Phase II Study of Cisplatin or Carboplatin for Triple-Negative Metastatic Breast Cancer and Evaluation of p63/p73 as a Biomarker of Response

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.

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.
Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Breast Cancer
  • 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 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.
    Other Name: Paraplatin
Experimental: Single Arm
Cisplatin or carboplatin (1 arm, 2 cohorts)
Interventions:
  • Drug: Cisplatin
  • Drug: carboplatin
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
86
June 2017
June 2014   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00483223
06-412
TBCRC009 ( Other Identifier: Translational Breast Cancer Research Consortium )
Yes
Not Provided
Plan to Share IPD: No
Steven Isakoff, MD, PhD, Massachusetts General Hospital
Massachusetts General Hospital
  • Beth Israel Deaconess Medical Center
  • Dana-Farber Cancer Institute
  • North Shore Medical Center
Principal Investigator: Steven Isakoff, MD, PhD Massachusetts General Hospital
Massachusetts General Hospital
July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP