Cisplatin vs. Doxorubicin/Cyclophosphamide in BrCa - Full Text View

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:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Cyclophosphamide Cisplatin Doxorubicin Doxorubicin hydrochloride

U.S. FDA Resources

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:	170
Study Start Date:	October 2012
Estimated Study Completion Date:	June 2018
Estimated Primary Completion Date:	June 2018 (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)

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Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
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
ER and PgR status by immunohistochemistry must be known. ER positive patients are allowed if physicain has determined neoadjuvant chemo is appropriate.
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 (unless not considered medically significant by the physician)
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, 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, District of Columbia
Georgetown University Medical Center	Recruiting
Washington D.C., District of Columbia, United States, 20007
Contact: Claudine Isaacs, MD isaacsc@georgetown.edu
United States, Maryland
Johns Hopkins	Recruiting
Baltimore, Maryland, United States, 21287
Contact: Antonio Wolff, MD awolff@jhmi.edu
United States, Massachusetts
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Contact: Steven Isakoff, MD, PhD 617-726-4920 sisakoff@partners.org
Principal Investigator: Steven Isakoff, MD, PhD
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
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
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
Rutgers 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, 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


Responsible Party:	Nadine Tung, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT01670500 History of Changes
Other Study ID Numbers:	12-258
Study First Received:	August 16, 2012
Last Updated:	August 30, 2016
Health Authority:	United States: Food and Drug Administration
Individual Participant Data
Plan to Share IPD:	No

Keywords provided by Dana-Farber Cancer Institute:


germline mutation BRCA1 mutation BRCA2 mutation

Additional relevant MeSH terms:


Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Liposomal doxorubicin Cisplatin Cyclophosphamide Doxorubicin Antineoplastic Agents Immunosuppressive Agents	Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Myeloablative Agonists Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 23, 2016