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Preoperative Cisplatin and Bevacizumab in ER-, PR-, HER2 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: March 22, 2017
Last verified: March 2017
  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 Estrogen Receptor (ER) negative, Progesterone Receptor (PR) negative and Human Epidermal Growth Factor Receptor 2 (HER2) 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: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase II Trial of Preoperative Cisplatin and Bevacizumab in Estrogen Receptor (ER) Negative, Progesterone (PR) Negative, Human Epidermal Growth Factor Receptor 2 (HER2) Negative Breast Cancer

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Pathologic Complete Response Rate After Preoperative Therapy With Cisplatin and Bevacizumab in ER-, PR-, Human Epidermal Growth Factor Receptor 2 (HER2) -Negative Early Breast Cancer. [ Time Frame: 2 years ]
    The goal of this measure was to determine the pathologic complete response rate (Miller-Payne (MP) score 5) after preoperative therapy with cisplatin and bevacizumab in ER-, PR-, HER2-negative early breast cancer.


Secondary Outcome Measures:
  • Clinical Overall and Complete Response Rates After Preoperative Therapy With Cisplatin and Bevacizumab [ Time Frame: 2 years ]
    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  • Toxicity of Administering Bevacizumab in Combination With Standard Adjuvant Chemotherapy. [ Time Frame: 2 years ]
    Number of patients who were unable to receive all cycles of chemotherapy on time for toxicity reasons.

  • Patients With Miller-Payne (MP) Score 3, 4, or 5 Response [ Time Frame: 2 years ]
    To describe a panel of molecular assays for an association with clinical response and, if feasible, with pathologic complete response (pCR) in ER-, PR-, HER2-negative subjects treated with cisplatin and bevacizumab in the preoperative setting. A Miller-Payne (MP) score of 3 indicates a decrease in the size of the cancer by 30% to 90%. A MP score of 4 indicates marked decrease in the size of the cancer by greater than 90%. A MP score of 5 indicates there is no residual cancer remaining (the same as a pathologic complete response).


Enrollment: 51
Study Start Date: September 2007
Estimated Study Completion Date: June 2017
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cisplatin/Avastin
Cisplatin 75mg/m2 every 3 weeks, neoadjuvant bevacizumab 15mg/m2 every 3 weeks, neoadjuvant doxorubicin, adjuvant (optional) cyclophosphamide , adjuvant (optional) paclitaxel, adjuvant (optional)
Drug: cisplatin
Preoperatively: Given intravenously on day one of the treatment cycle (once every 3 weeks) for four cycles
Other Name: platinol
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
Other Name: Avastin
Drug: doxorubicin
Postoperative: Given intravenously for four 2-week cycles
Other Name: adriamycin
Drug: cyclophosphamide
Postoperative: Given intravenously for four two-week cycles
Other Name: cytoxan
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)
Other Name: taxol

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, Electrocardiogram (EKG) and an Magnetic Resonance Imaging (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, multiple gated acquisition scan (MUGA) or Echocardiogram Scans, and a hearing test.
  Eligibility

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

Inclusion Criteria:

  • All tumors must be ER-, PR- and HER2-negative
  • Clinical stage T2 or T3, N0-3, M0. 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 (PS) 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 ductal carcinoma in situ (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
  • New York Heart Association (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 central nervous system (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
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
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 Texas Oncology-The Woodlands
  More Information

Responsible Party: Steven Isakoff, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00580333     History of Changes
Other Study ID Numbers: 06-202
AVF36335 ( Other Identifier: Genentech )
Study First Received: December 20, 2007
Results First Received: April 2, 2014
Last Updated: March 22, 2017
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Massachusetts General Hospital:
ER negative
PR negative
HER2 negative

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Liposomal doxorubicin
Albumin-Bound Paclitaxel
Doxorubicin
Cyclophosphamide
Cisplatin
Bevacizumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on April 25, 2017