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Cisplatin vs. Doxorubicin/Cyclophosphamide in BrCa

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ClinicalTrials.gov Identifier: NCT01670500
Recruitment Status : Active, not recruiting
First Posted : August 22, 2012
Last Update Posted : March 5, 2019
Sponsor:
Information provided by (Responsible Party):
Nadine Tung, MD, Dana-Farber Cancer Institute

Study Description
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Brief Summary:

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 or disease Intervention/treatment Phase
Breast Cancer Drug: Cisplatin Drug: Cyclophosphamide Drug: Doxorubicin Phase 2

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : October 2012
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
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)


Outcome Measures
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Primary Outcome Measures :
  1. pCR to neoadjuvant cisplatin vs. pCR to AC [ Time Frame: 3 years ]
    To determine if the pathologic complete response (pCR) rate (determined by the Miller-Payne method) [pCR in breast and nodes (i.e. RCB 0) or pCR in breast (i.e. Miller Payne 5) if nodes are not evaluable (i.e. positive nodes were removed surgically before chemo)] 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 :
  1. Residual Cancer Burden after neoadjuvant cisplatin or AC [ Time Frame: 2 years ]
    To determine Residual Cancer Burden (RCB) and compare the rates of RCB 0 as well as RCB 0 and RCB 1 (combined, with the inclusion of pCR in the breast when nodes are not evaluable, i.e. Miller-Payne 5 when positive nodes were removed prior to chemo) after neoadjuvant cisplatin or doxorubicin/ cyclophosphamide (AC) in women with newly diagnosed breast cancer and a germline BRCA mutation.

  2. Clinical response rate [ Time Frame: 2 years ]
    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.

  3. Comparison of toxicities of cisplatin and AC [ Time Frame: 2 years ]
    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.

  4. Collection of pre-chemotherapy biopsies [ Time Frame: 3 years ]
    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.

  5. Comparison of Miller Payne 4 and 5 rates [ Time Frame: 3 years ]
    To compare the rates of Miller Payne 4 (near pCR) and 5 (near pCR) combined between those subjects who received neoadjuvant cisplatin and those who received neoadjuvant AC.


Eligibility Criteria
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Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologic confirmation of invasive breast cancer
  • Stage: Clinical T1 >/= 1.0 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 anthracycline or platinum based therapy
  • 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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01670500


Locations
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United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
United States, Connecticut
Smilow Cancer Hospital Care Center at Derby
Derby, Connecticut, United States, 06418
Smilow Cancer Hospital Care Center at Guilford
Guilford, Connecticut, United States, 06437
St. Francis Hospital and Medical Center
Hartford, Connecticut, United States, 06105
Yale School of Medicine
New Haven, Connecticut, United States, 06520
United States, District of Columbia
Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
Sibley Memorial Hospital
Washington, District of Columbia, United States, 20016-2698
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New Jersey
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27708
United States, Rhode Island
Women and Infants Hospital
Providence, Rhode Island, United States, 02905
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Investigators
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Principal Investigator: Nadine Tung, MD Beth Israel Deaconess Medical Center
More Information
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Responsible Party: Nadine Tung, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01670500     History of Changes
Other Study ID Numbers: 12-258
First Posted: August 22, 2012    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Nadine Tung, MD, Dana-Farber Cancer Institute:
germline mutation
BRCA1 mutation
BRCA2 mutation

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cisplatin
Cyclophosphamide
Doxorubicin
Liposomal 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