Cisplatin vs. Doxorubicin/Cyclophosphamide in BrCa

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Dana-Farber Cancer Institute
Sponsor:
Information provided by (Responsible Party):
Nadine Tung, MD, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT01670500
First received: August 16, 2012
Last updated: March 16, 2014
Last verified: March 2014
  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)

  Hide Detailed Description

Detailed Description:

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.

  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
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, see Learn About Clinical Studies.

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 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 Recruiting
Aurora, Colorado, United States, 80045
Contact: Virginia Borges, MD    303-724-0186    virginia.borges@ucdenver.edu   
United States, Connecticut
Yale School of Medicine 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 Withdrawn
Boston, Massachusetts, United States, 02130
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 Hampshire
New Hampshire Oncology-Hematology Recruiting
Hooksett, New Hampshire, United States, 03106
Contact: Douglas Weckstein, MD    603-622-6484    d.weckstein@nhoh.com   
United States, New Jersey
The Cancer Institute of New Jersey 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 Recruiting
Providence, Rhode Island, United States, 02905
Contact: Robert Legare, MD    401-453-7540    rlegare@wihri.org   
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Banu Arun, MD    713-792-2817    barun@mdanderson.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: March 16, 2014
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
Liposomal doxorubicin
Cisplatin
Cyclophosphamide
Doxorubicin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing 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

ClinicalTrials.gov processed this record on August 28, 2014