Cisplatin vs. Doxorubicin/Cyclophosphamide in BrCa
This study is currently recruiting participants.
Verified October 2012 by Dana-Farber Cancer Institute
Sponsor:
Beth Israel Deaconess Medical Center
Information provided by (Responsible Party):
Nadine Tung, MD, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT01670500
First received: August 16, 2012
Last updated: October 26, 2012
Last verified: October 2012
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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
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 | Not yet 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 | Not yet recruiting |
| Aurora, Colorado, United States, 80045 | |
| Contact: Virginia Borges, MD 303-724-0186 virginia.borges@ucdenver.edu | |
| United States, Connecticut | |
| Yale School of Medicine | Not yet recruiting |
| New Haven, Connecticut, United States, 06520 | |
| Contact: Erin Hofstatter, MD 203-737-1600 erin.hofstatter@yale.edu | |
| United States, Massachusetts | |
| 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 | |
| Dana-Farber Cancer Institute at Faulkner Hospital | Not yet recruiting |
| Boston, Massachusetts, United States, 02130 | |
| Contact: Erica Mayer, MD 617-632-2335 emayer@partners.org | |
| Principal Investigator: Erica Mayer, MD, MPH | |
| 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 Jersey | |
| The Cancer Institute of New Jersey | Not yet 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 | Not yet recruiting |
| Providence, Rhode Island, United States, 02905 | |
| Contact: Robert Legare, MD 401-453-7540 rlegare@wihri.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: | October 26, 2012 |
| 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 Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Cisplatin Cyclophosphamide Doxorubicin Antineoplastic Agents Therapeutic Uses Pharmacologic Actions |
Radiation-Sensitizing Agents Physiological Effects of Drugs Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Myeloablative Agonists Antibiotics, Antineoplastic |
ClinicalTrials.gov processed this record on May 21, 2013