Cisplatin vs. Doxorubicin/Cyclophosphamide in BrCa
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01670500|
Recruitment Status : Active, not recruiting
First Posted : August 22, 2012
Last Update Posted : May 8, 2020
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|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||118 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Primary Completion Date :||May 2019|
|Estimated Study Completion Date :||April 2022|
Active Comparator: Doxorubicin-Cyclophosphamide
Doxorubicin q 2-3 wk x 4 Cyclophosphamide q 2-3 wk x 4
administered with doxorubicin intravenously every 2 or 3 weeks for 4 doses
Other Name: Cytoxan
administered with Cyclophosphamide intravenously every 2 or 3 weeks for 4 doses
Other Name: Adriamycin
Active Comparator: Cisplatin
Cisplatin q 3 wk x 4
administered intravenously every 3 weeks for 4 doses
Other Name: cisplatinum, or cis-diamminedichloroplatinum(II) (CDDP)
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Recurrence Free Survival (RFS) after cisplatin or AC [ Time Frame: 3 years ]To determine if 3-year recurrence free survival is significantly better for germline BRCA mutation (gBRCAm) carriers with newly diagnosed HER2-negative breast cancer allocated to cisplatin vs. AC chemotherapy
- Recurrence Free Survival (RFS) with pathologic complete response (pCR) vs. RFS with no pCR [ Time Frame: 3 years ]To determine if 3-year recurrence free survival is significantly improved for gBRCAm carriers who achieved pCR with those who did not.
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
|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|
|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|
|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|
|Principal Investigator:||Nadine Tung, MD||Beth Israel Deaconess Medical Center|