Cisplatin vs. Doxorubicin/Cyclophosphamide in BrCa
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.
|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|
- 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.
- 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.
|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)|
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: CytoxanDrug: 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
administered intravenously every 3 weeks for 4 doses
Other Name: cisplatinum, or cis-diamminedichloroplatinum(II) (CDDP)
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If screening tests show that you are eligible to participate in the research study you will begin study treatment. You will undergo a research biopsy so the study team can obtain tissue samples. This will be used for biomarker research and will help your doctors to better understand your disease, how the drug is working in your body, and may help to identify which people may benefit most from platinum or from adriamycin/cytoxan in the future.
Because no one knows which of the study options is best, you will be "randomized" to receive either cisplatin or doxorubicin and cyclophosphamide ("AC") chemotherapy prior to removal of your breast cancer. Chemotherapy administered before the removal of the cancer is known as neoadjuvant chemotherapy. Randomization means that you are put into a group by chance. It is like flipping a coin. Neither you nor the research doctor will choose what group you will be in. You will have an equal chance of being placed in either group.
If you are randomized to receive cisplatin you will receive cisplatin once every three weeks for a total of four doses. You will be given cisplatin by vein (IV) on the first day of each treatment cycle. The cisplatin infusion can take between 1 to 2 hours. Before and after receiving cisplatin, you will receive fluid hydration by vein, and you will also be given medicine to help prevent side effects such as nausea. The total time of the infusion of cisplatin and the additional fluid and medications will take about 6 hours. After you receive cisplatin, you will be asked to drink about 12 eight ounce glasses of fluid per day, especially 2 or 3 days after therapy. The study treatment will stop if you have serious side effects or if the tumor grows despite receiving cisplatin chemotherapy.
If you are randomized to "AC" chemotherapy you will receive both doxorubicin and cyclophosphamide once every 2 or 3 weeks for a total of four doses by vein on the first day of each treatment cycle. The interval between chemotherapy will be decided by your research doctor. If you receive the chemotherapy every two weeks, you will also receive a subcutaneous injection the day after chemotherapy. This injection contains a medicine that contains a growth factor that will boost your immune system in order to allow your body to be ready for chemotherapy in two weeks. The study treatment will be stopped if you have serious side effects or if the tumor grows despite the doxorubicin and cyclophosphamide chemotherapy.
At the beginning of each treatment cycle you will have a physical exam (including weight and vital signs) and you will be asked general questions about your health and any medications you may be taking, as well as specific questions about any side effects you may be experiencing while receiving study treatment. Prior to each cycle of chemotherapy, you will have standard blood tests to check your blood counts. If you are receiving cisplatin your kidney function and body salts will also be checked prior to each chemotherapy cycle. In addition, 7-10 days after chemotherapy your blood will be drawn to look at your blood cell count to determine your risk of infection; if you have received cisplatin, your kidney function and blood electrolytes will also be evaluated. The blood draw performed 7-10 days after chemotherapy can be done in the hospital where you received your chemotherapy or closer to home. About 1 tablespoon of blood will be drawn for these tests.
Surgery to remove your tumor will occur within six weeks after the last dose of chemotherapy. Your surgery will be performed by your surgeon, as part of the standard care for your disease.
Your treating physician or nurse practitioner will examine you to assess your tumor each time you receive chemotherapy. A measurement of your tumor will be performed on the first day of each treatment cycle as part of your physical exam. After the slides of your initial breast cancer biopsy have been reviewed at your hospital, these slides and your tumor block will be sent to the study pathologist at Beth Israel Deaconess Medical Center. Likewise, after chemotherapy, your breast cancer will be removed by lumpectomy or mastectomy. After these slides are reviewed at your hospital, they will also be sent with the tumor block to the study pathologist so that the response of your tumor to the study treatment can be assessed. After these slides are reviewed, they will be returned to the hospital at which the biopsy and surgery were performed.
Decisions about whether you will receive more chemotherapy after your surgery is up to your treating physicians. If you receive chemotherapy, the choice of chemotherapy is also up to your doctors. Decisions about post-operative chemotherapy are not part of this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01670500
|Contact: Nadine Tung, MDfirstname.lastname@example.org|
|United States, California|
|Cedars Sinai Hospital||Recruiting|
|Los Angeles, California, United States, 90048|
|Contact: William Audeh, MD 310-423-1188 email@example.com|
|United States, Colorado|
|University of Colorado Cancer Center||Recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Virginia Borges, MD 303-724-0186 firstname.lastname@example.org|
|United States, Connecticut|
|Yale School of Medicine||Recruiting|
|New Haven, Connecticut, United States, 06520|
|Contact: Erin Hofstatter, MD 203-737-1600 email@example.com|
|United States, District of Columbia|
|Georgetown University Medical Center||Recruiting|
|Washington D.C., District of Columbia, United States, 20007|
|Contact: Claudine Isaacs, MD firstname.lastname@example.org|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Steven Isakoff, MD, PhD 617-726-4920 email@example.com|
|Principal Investigator: Steven Isakoff, MD, PhD|
|Dana-Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Judy Garber, MD, MPH 617-632-2282 firstname.lastname@example.org|
|Principal Investigator: Judy Garber, MD, MPH|
|Beth Israel Deaconess Medical Center||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Nadine Tung, MD 617-667-7081 email@example.com|
|Principal Investigator: Nadine Tung, MD|
|Dana-Farber Cancer Institute at Faulkner Hospital||Withdrawn|
|Boston, Massachusetts, United States, 02130|
|United States, New Hampshire|
|New Hampshire Oncology-Hematology||Recruiting|
|Hooksett, New Hampshire, United States, 03106|
|Contact: Douglas Weckstein, MD 603-622-6484 firstname.lastname@example.org|
|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 email@example.com|
|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 firstname.lastname@example.org|
|United States, Pennsylvania|
|University of Pennsylvania Abramson Cancer Center||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Susan Domchek, MD 215-615-3360 email@example.com|
|United States, Rhode Island|
|Women and Infants Hospital||Recruiting|
|Providence, Rhode Island, United States, 02905|
|Contact: Robert Legare, MD 401-453-7540 firstname.lastname@example.org|
|United States, Texas|
|MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Banu Arun, MD 713-792-2817 email@example.com|
|Principal Investigator:||Nadine Tung, MD||Beth Israel Deaconess Medical Center|