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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01670500
Recruitment Status : Recruiting
First Posted : August 22, 2012
Last Update Posted : September 5, 2018
Information provided by (Responsible Party):
Nadine Tung, MD, Dana-Farber Cancer Institute

Brief Summary:

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

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Detailed Description:

If screening tests show that you are eligible to participate in the research study you will begin study treatment. You may undergo an optional 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 DF/HCC. 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : October 2012
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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)

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Pathologic confirmation of invasive breast cancer
  • Stage: Clinical T1 >/= 1.0 cm, T2 or T3, N0-3, M0
  • HER2 negative
  • ER and PgR status by immunohistochemistry must be known. ER positive patients are allowed if physicain has determined neoadjuvant chemo is appropriate.
  • Life expectancy greater than six months
  • Use of an effective means of contraception is required

Exclusion Criteria:

  • Pregnant or breastfeeding
  • Prior anthracycline or platinum based therapy
  • 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 (unless not considered medically significant by the physician)
  • Known HIV positive individuals on combination antiretroviral therapy

Information from the National Library of Medicine

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 identifier (NCT number): NCT01670500

Contact: Nadine Tung, MD 6176677081

United States, Colorado
University of Colorado Cancer Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Virginia Borges, MD    303-724-0186   
United States, Connecticut
Smilow Cancer Hospital Care Center at Derby Recruiting
Derby, Connecticut, United States, 06418
Contact: Erin Hofstatter, MD   
Smilow Cancer Hospital Care Center at Guilford Recruiting
Guilford, Connecticut, United States, 06437
Contact: Erin Hofstatter, MD   
St. Francis Hospital and Medical Center Recruiting
Hartford, Connecticut, United States, 06105
Contact: Erin Hofstatter, MD   
Yale School of Medicine Recruiting
New Haven, Connecticut, United States, 06520
Contact: Erin Hofstatter, MD    203-737-1600   
United States, District of Columbia
Georgetown University Medical Center Recruiting
Washington, District of Columbia, United States, 20007
Contact: Claudine Isaacs, MD   
Sibley Memorial Hospital Recruiting
Washington, District of Columbia, United States, 20016-2698
Contact: Antonio Wolff, MD   
United States, Maryland
Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21287
Contact: Antonio Wolff, MD   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Steven Isakoff, MD, PhD    617-726-4920   
Principal Investigator: Steven Isakoff, MD, PhD         
Dana-Farber Cancer Institute at Faulkner Hospital Withdrawn
Boston, Massachusetts, United States, 02130
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Nadine Tung, MD    617-667-7081   
Principal Investigator: Nadine Tung, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Judy Garber, MD, MPH    617-632-2282   
Principal Investigator: Judy Garber, MD, MPH         
United States, New Hampshire
New Hampshire Oncology-Hematology Withdrawn
Hooksett, New Hampshire, United States, 03106
United States, New Jersey
Rutgers Cancer Institute of New Jersey Active, not recruiting
New Brunswick, New Jersey, United States, 08901
United States, New York
Memorial Sloan-Kettering Cancer Center Withdrawn
New York, New York, United States, 10065
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27708
Contact: P. Kelly Marcom   
United States, Rhode Island
Women and Infants Hospital Recruiting
Providence, Rhode Island, United States, 02905
Contact: Robert Legare, MD    401-453-7540   
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Banu Arun, MD    713-792-2817   
MD Anderson in Katy Withdrawn
Houston, Texas, United States, 77094
MD Anderson in the Bay Area Withdrawn
Nassau Bay, Texas, United States, 77058
MD Anderson - Sugar Land Withdrawn
Sugar Land, Texas, United States, 77478
MD Anderson - The Woodlands Withdrawn
The Woodlands, Texas, United States, 77384
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Principal Investigator: Nadine Tung, MD Beth Israel Deaconess Medical Center

Responsible Party: Nadine Tung, MD, Principal Investigator, Dana-Farber Cancer Institute Identifier: NCT01670500     History of Changes
Other Study ID Numbers: 12-258
First Posted: August 22, 2012    Key Record Dates
Last Update Posted: September 5, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Nadine Tung, MD, Dana-Farber Cancer Institute:
germline mutation
BRCA1 mutation
BRCA2 mutation

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Liposomal doxorubicin
Antineoplastic 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