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

NCT00483223 | Completed Phase 2 Results DMC

• 2 other identifiers: 06-412TBCRC009
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 10

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.

Conditions

Breast Cancer

Keywords

ER negative; PgR negative; HER2 negative; cisplatin; carboplatinum; platinum; p63; p73

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate

  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

  3 years

• Response Rate Categorized by p63/p73 Ratio

  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).

  3 years

Secondary Outcomes (2)

• Objective Response Rate Categorized by Subgroup

  3 years

• Progression Free Survival and Overall Survival

  5 years

Study Arms (1)

Single Arm

EXPERIMENTAL

Cisplatin or carboplatin (1 arm, 2 cohorts)

Drug: Cisplatin; Drug: carboplatin

Interventions

Cisplatin 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.

Also known as: Platinol

Single Arm

carboplatin 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.

Also known as: Paraplatin

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Beth Israel Deaconess Medical Center: collaborator
• Dana-Farber Cancer Institute: collaborator
• North Shore Medical Center: collaborator

Study Sites (10)

University of Alabama-Birmingham

Birmingham, Alabama, United States

Location

UCSF

San Francisco, California, United States

Location

Georgetown - Lombardi Cancer Center

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

Location

Johns Hopkins University Medical Center

Baltimore, Maryland, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

North Shore Medical Center

Peabody, Massachusetts, 01960, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Location

University of North Carolina

Chapel Hill, North Carolina, United States

Location

Related Publications (1)

• 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.

  PMID: 25847936 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Ectrodactyly, Ectodermal Dysplasia, and Cleft Lip-Palate Syndrome 3

Interventions

Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Steven Isakoff, MD, PhD
• Organization: Massachusetts General Hospital

SISAKOFF@mgh.harvard.edu

617-726-4920

Study Officials

• Steven Isakoff, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Physician

Study Record Dates

• First Submitted: June 5, 2007
• First Posted: June 6, 2007
• Study Start: June 1, 2007
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2017
• Last Updated: August 25, 2017
• Results First Posted: June 1, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)