Clinical trial NCT00580333: Preoperative Cisplatin and Bevacizumab in ER-, PR-, HER2 Negative Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: ER negative
PR negative
HER2 negative
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Dana-Farber Cancer Institute
name: Beth Israel Deaconess Medical Center
name: Brigham and Women's Hospital
name: Genentech, Inc.
First posted: 2007-12-24
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: 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.
timeFrame: 2 years
Secondary outcomes:
measure: Clinical Overall and Complete Response Rates After Preoperative Therapy With Cisplatin and Bevacizumab
timeFrame: 2 years
measure: Toxicity of Administering Bevacizumab in Combination With Standard Adjuvant Chemotherapy.
timeFrame: 2 years
measure: Patients With Miller-Payne (MP) Score 3, 4, or 5 Response
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Texas Oncology-The Woodlands
name: Paula D. Ryan, MD
role: PRINCIPAL_INVESTIGATOR
References: