Cisplatin vs. Doxorubicin/Cyclophosphamide in BrCa

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Dana-Farber Cancer Institute
Sponsor:
Information provided by (Responsible Party):
Nadine Tung, MD, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT01670500
First received: August 16, 2012
Last updated: March 16, 2014
Last verified: March 2014
  Purpose

This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational drug, which is cisplatin in this trial, to learn how well it works in treating a specific cancer. "Investigational" means that cisplatin is still being studied for use in this setting and that research doctors are trying to find out more about it-in this case, how effective cisplatin is for treating breast cancer in BRCA mutation carriers. It also means that the FDA has not yet approved cisplatin for your type of cancer. Cisplatin has been approved by the FDA for treatment of other cancers.

The purpose of this study is to evaluate cisplatin, a chemotherapy drug that has been shown to be active in the treatment of women with breast cancer and a BRCA mutation. In this study, we are comparing cisplatin to the standard chemotherapy, doxorubicin and cyclophosphamide ("AC") that you might receive if you did not participate in this study.


Condition Intervention Phase
Breast Cancer
Drug: Cisplatin
Drug: Cyclophosphamide
Drug: Doxorubicin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Neoadjuvant Cisplatin vs. Doxorubicin/Cyclophosphamide (AC) in Women With Newly Diagnosed Breast Cancer and Germline BrCa Mutations

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • pCR to neoadjuvant cisplatin vs. pCR to AC [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To determine if the pathologic complete response (pCR) rate (determined by the Miller-Payne method) to neoadjuvant cisplatin is at least 20% greater than the pCR to doxorubicin/cyclophosphamide (AC) in women with newly diagnosed breast cancer and a germline BRCA mutation.


Secondary Outcome Measures:
  • Residual Cancer Burden after neoadjuvant cisplatin or AC [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the Residual Cancer Burden (RCB) after neoadjuvant cisplatin or doxorubicin/cyclophosphamide (AC) in women with newly diagnosed breast cancer and a germline BRCA mutation.

  • Clinical response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the clinical response rate, defined as the number of partial and complete responses, after preoperative therapy with either cisplatin or AC in participants with germline BRCA mutation and breast cancer.

  • Comparison of toxicities of cisplatin and AC [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To compare the toxicities of cisplatin and AC preoperative chemotherapy in BRCA mutation carriers with newly diagnosed breast cancer. Toxicities including (but not limited to) hematologic, GI (e.g., Nausea/vomitting), renal and neurologic will be assessed.

  • Collection of pre-chemotherapy biopsies [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Pretreatment tumor biopsies will be analyzed using genome wide SNP profiling to determine number of regions of telomeric allelic imbalance (NtAI) and chromosome 15q26 copy number, and chromosome 8q22 copy number. Tumor sections will be examined for gene amplifications, losses and NtAI in tumors. Gene expression profiling will be performed to determine intrinsic subtype (basal-like, claudin-low, etc.) and to measure biomarker genes including BLM and FANCI associated with cisplatin sensitivity or LAPTM4B and YWHAZ associated with anthracycline resistance. Exploratory analysis will be performed to seek new measures of therapy response using the data from DNA copy number and gene expression profiles. In addition, we will plan to perform whole exome and possibly whole genome sequencing of tumors to identify potential modifiers of response to therapy.


Estimated Enrollment: 166
Study Start Date: October 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Doxorubicin-Cyclophosphamide
Doxorubicin q 2-3 wk x 4 Cyclophosphamide q 2-3 wk x 4
Drug: Cyclophosphamide
administered with doxorubicin intravenously every 2 or 3 weeks for 4 doses
Other Name: Cytoxan
Drug: Doxorubicin
administered with Cyclophosphamide intravenously every 2 or 3 weeks for 4 doses
Other Name: Adriamycin
Active Comparator: Cisplatin
Cisplatin q 3 wk x 4
Drug: Cisplatin
administered intravenously every 3 weeks for 4 doses
Other Name: cisplatinum, or cis-diamminedichloroplatinum(II) (CDDP)

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Pathologic confirmation of invasive breast cancer
  • Stage: Clinical T1 > 1.5 cm, T2 or T3, N0-3, M0
  • HER2 negative
  • If tumor is ER+, it must be grade 2 or 3 or must have oncotype recurrence score > 31
  • ER and PgR status by immunohistochemistry must be known
  • Life expectancy greater than six months
  • Use of an effective means of contraception is required

Exclusion Criteria:

  • Pregnant or breastfeeding
  • Prior chemotherapy at any time
  • Prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation or experimental therapy
  • Ipsilateral breast recurrence, unless prior treatment consisted of excision alone for DCIS or breast-conserving treatment and hormonal therapy for DCIS or invasive cancer
  • Peripheral neuropathy of any etiology that exceeds grade 1
  • Significant hearing loss
  • Renal dysfunction
  • Use of other investigational or study agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs
  • Uncontrolled intercurrent illness
  • Any condition that would prohibit administration of corticosteroids
  • Uncontrolled diabetes
  • Pre-existing medical condition that would represent toxicity in excess of grade 1 as measured by CTCAE
  • Known HIV positive individuals on combination antiretroviral therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01670500

Contacts
Contact: Nadine Tung, MD 6176677081 ntung@bidmc.harvard.edu

Locations
United States, California
Cedars Sinai Hospital Recruiting
Los Angeles, California, United States, 90048
Contact: William Audeh, MD    310-423-1188    william.audeh@cshs.org   
United States, Colorado
University of Colorado Cancer Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Virginia Borges, MD    303-724-0186    virginia.borges@ucdenver.edu   
United States, Connecticut
Yale School of Medicine Recruiting
New Haven, Connecticut, United States, 06520
Contact: Erin Hofstatter, MD    203-737-1600    erin.hofstatter@yale.edu   
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Judy Garber, MD, MPH    617-632-2282    jegarber@partners.org   
Principal Investigator: Judy Garber, MD, MPH         
Dana-Farber Cancer Institute at Faulkner Hospital Withdrawn
Boston, Massachusetts, United States, 02130
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Nadine Tung, MD    617-667-7081    ntung@bidmc.harvard.edu   
Principal Investigator: Nadine Tung, MD         
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Steven Isakoff, MD, PhD    617-726-4920    sisakoff@partners.org   
Principal Investigator: Steven Isakoff, MD, PhD         
United States, New Hampshire
New Hampshire Oncology-Hematology Recruiting
Hooksett, New Hampshire, United States, 03106
Contact: Douglas Weckstein, MD    603-622-6484    d.weckstein@nhoh.com   
United States, New Jersey
The Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08901
Contact: Deborah Toppmeyer, MD    732-235-6789    toppmede@umdnj.edu   
United States, New York
Memorial Sloan-Kettering Cancer Center Not yet recruiting
NY, New York, United States, 10065
Contact: Mark Robson, MD    646-888-4058    robsonm@mskcc.org   
United States, Pennsylvania
University of Pennsylvania Abramson Cancer Center Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Susan Domchek, MD    215-615-3360    susan.domchek@uphs.upenn.edu   
United States, Rhode Island
Women and Infants Hospital Recruiting
Providence, Rhode Island, United States, 02905
Contact: Robert Legare, MD    401-453-7540    rlegare@wihri.org   
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Banu Arun, MD    713-792-2817    barun@mdanderson.org   
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Investigators
Principal Investigator: Nadine Tung, MD Beth Israel Deaconess Medical Center
  More Information

No publications provided

Responsible Party: Nadine Tung, MD, Principal Investigator, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01670500     History of Changes
Other Study ID Numbers: 12-258
Study First Received: August 16, 2012
Last Updated: March 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
germline mutation
BRCA1 mutation
BRCA2 mutation

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Cisplatin
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Alkylating Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 29, 2014