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Preoperative Cisplatin and Bevacizumab in ER-, PR-, Her-2 Negative Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Genentech, Inc.
Information provided by (Responsible Party):
Steven Isakoff, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00580333
First received: December 20, 2007
Last updated: April 29, 2013
Last verified: April 2013
  Purpose

The purpose of this study is to find out what effect taking cisplatin in combination with bevacizumab before surgery and then standard chemotherapy plus bevacizumab after surgery will have on participants with ER negative, PR negative and HER-2 negative breast cancer. Cisplatin is used to destroy cancer cells in many types of cancers, and has shown to be effective and have manageable side effects. Bevacizumab is an antibody, which is a protein that attacks a foreign substance in the body. Bevacizumab slows or stops cell growth in cancerous tumors by decreasing the blood supply to the tumors.


Condition Intervention Phase
Breast Cancer
Drug: cisplatin
Drug: bevacizumab
Drug: doxorubicin
Drug: cyclophosphamide
Drug: paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Preoperative Cisplatin and Bevacizumab in ER-, PR-, Her-2 Negative Breast Cancer

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • To determine the pathologic complete response rate after preoperative therapy with cisplatin and bevacizumab in ER-, PR-, HER2-negative early breast cancer. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the clinical response rate, defined as the number of partial and complete responses, after preoperative therapy with cisplatin and bevacizumab in this patient population. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To determine the feasibility and toxicity of administering bevacizumab in combination with standard adjuvant chemotherapy. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • To describe a panel of molecular assays for an association with clinical response and, if feasible, with pathologic complete response in ER-, PR-, HER2-negative subjects treated with cisplatin and bevacizumab in the preoperative setting. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: September 2007
Estimated Study Completion Date: December 2013
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cisplatin/Avastin Drug: cisplatin
Preoperatively: Given intravenously on day one of the treatment cycle (once every 3 weeks) for four cycles
Drug: bevacizumab
Preoperatively: Given intravenously on day 1 of the treatment cycle (once every three weeks) for three cycles Postoperatively: Intravenously for four 2-week cycles (once every two weeks) and after the 8 weeks (study doctor will determine course of treatment) for an additional four 2-week cycles with or with out paclitaxel
Drug: doxorubicin
Postoperative: Given intravenously for four 2-week cycles
Drug: cyclophosphamide
Postoperative: Given intravenously for four two-week cycles
Drug: paclitaxel
Postoperative: 8 weeks after postoperative chemotherapy regimen (study doctor will determine course of treatment) paclitaxel for four 2-week cycles (once every two weeks)

Detailed Description:
  • To prepare for surgery, a small "clip" will be placed into the tumor area so that the surgeon can locate the site of the tumor at the time of surgery. This is a standard procedure for breast cancer.
  • The study drugs will be given in four 3-week cycles (about 3 months). Participants will come into the clinic each day they receive study treatment intravenously. Cisplatin will be given on day one of the treatment cycle (once every 3 weeks) for four cycles. Bevacizumab will be given on day one of the treatment cycle for three cycles.
  • On day one of each 3-week cycle a physical exam, routine blood tests and urine test will be performed. 7-8 days after chemotherapy, blood tests and a hearing test will be performed. A preoperative study visit will take place 7-10 days before surgery and a physical exam, routine blood tests, EKG and an MRI of the breast will be performed.
  • Surgery to remove the tumor will occur at least three weeks after the last dose of cisplatin and is considered standard of care.
  • Postoperative chemotherapy will begin at least three weeks after surgery. Everyone on the research study will receive four 2-week cycles of doxorubicin and cyclophosphamide plus bevacizumab. After the 8 weeks, the doctor will decide which of the following two treatment regimens the participant will receive: Bevacizumab for four 2-week cycles (once every two weeks) or; Paclitaxel plus bevacizumab for four 2-week cycles (once every two weeks).
  • At the end of the postoperative chemotherapy, the participant will return to the clinic for a medical history, physical exam, vital signs, performance status, routine blood tests, MUGA or Echo Scans, and a hearing test.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All tumors must be ER-, PR- and HER2-negative
  • Clinical stage T2 or T3, NO-3, MO. Subjects with inflammatory breast cancer are not eligible
  • For subjects with clinically negative axilla, a sentinel lymph node biopsy will be performed either up front or after preoperative therapy at the discretion of the subject's physicians; for subjects with a clinically positive axilla, a needle aspiration or core biopsy will be performed to confirm the presence of metastatic disease in the lymph nodes.
  • 18 years of age or older
  • Performance status of 0 or 1
  • Use of an effective means of contraception in subjects of child-bearing potential
  • Normal organ function as described in the protocol

Exclusion Criteria:

  • Any prior cytotoxic chemotherapy or radiation for the current breast cancer
  • HER2-negative ipsilateral breast recurrence, unless prior treatment consisted of excision alone for DCIS or breast-conserving treatment and hormonal therapy for DCIS or invasive cancer
  • Life expectancy of less than 12 weeks
  • Current, recent, or planned participation in an experimental durg study other than a Genentech-sponsored bevacizumab cancer study
  • Renal dysfunction for which exposure to cisplatin would require dose modifications
  • Steroid dependent asthma
  • Peripheral neuropathy of any etiology that exceeds grade 1
  • Uncontrolled diabetes
  • History of malignancy treated without curative intent
  • Any other pre-existing medical condition that would represent toxicity in excess of grade 1
  • Inadequately controlled hypertension
  • Any prior history of hypertensive crisis or hypertensive encephalopathy
  • NYHA Grade II or greater congestive hear failure
  • History of myocardial infarction or unstable angina within 12 months prior to study enrollment
  • Any history of stroke or transient ischemic attack at any time
  • Known CNS disease
  • Significant vascular disease
  • Symptomatic peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • Major surgical procedure, open biopsy, or significant traumatic injury within 21 days prior to study enrollment
  • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study enrollment
  • Serious, non-healing wound, ulcer or bone fracture
  • Proteinuria at screening
  • Known hypersensitivity to any component of bevacizumab
  • Pregnant or lactating
  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: NCT00580333

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Genentech, Inc.
Investigators
Principal Investigator: Paula D. Ryan, MD Fox Chase Cancer Center
  More Information

No publications provided

Responsible Party: Steven Isakoff, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00580333     History of Changes
Other Study ID Numbers: 06-202, AVF36335
Study First Received: December 20, 2007
Last Updated: April 29, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
ER negative
PR negative
HER-2 negative

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Bevacizumab
Cisplatin
Cyclophosphamide
Paclitaxel
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 25, 2014