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
Results First Posted : August 3, 2020
Last Update Posted : September 1, 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)
- Rate of Pathologic Complete Response (pCR) [ Time Frame: 3 years ]Pathologic complete response (pCR) rate (determined by the Miller-Payne method) in doxorubicin-cyclophosphamide vs cisplatin arms.
- Rate of Residual Cancer Burden (RCB) 0/1 [ Time Frame: 2 years ]Residual Cancer Burden (RCB) rate of RCB 0 or 1 in participants receiving Doxorubicin-Cyclophosphamide vs participants receiving Cisplatin.
- Clinical Response Rate [ Time Frame: 3 years ]
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.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or ultrasound: Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) is >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
- Number of Grade 3 and Grade 4 Adverse Events [ Time Frame: 2 years ]Comparison of toxicities for cisplatin and AC preoperative chemotherapy in BRCA mutation carriers with newly diagnosed breast cancer, reported as number of all Grade 3 and 4 adverse events and number of non-hematologic Grade 3 and 4 adverse events.
- Analysis of Pre-chemotherapy Biopsies [ Time Frame: 5 years ]Biopsies collected for future analyses of biomarkers that predict for response to cisplatin or AC chemotherapy in BRCA mutation carriers. 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.
- Rate of Miller Payne 4 and 5 [ Time Frame: 3 years ]
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.
Miller Payne 4: a marked disappearance of tumor cells (more than 90%) such that only small clusters or widely dispersed individual cells remain (almost pCR);
Miller Payne 5: no malignant cells identifiable in sections from the site of the tumor (pCR)
- Rate of Recurrence Free Survival (RFS) After Cisplatin or AC [ Time Frame: 5 years ]Rate of 3-year recurrence free survival in doxorubicin-cyclophosphamide and cisplatin arms for germline BRCA mutation (gBRCAm) carriers with newly diagnosed HER2-negative breast cancer
- Rate of Recurrence Free Survival (RFS) With Pathologic Complete Response (pCR) vs. With no pCR [ Time Frame: 5 years ]Rate of 3-year recurrence free survival 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|