Phase II Study of Carboplatin and Bevacizumab (Avastin) for ER Neg, PR Neg, and HER2/Neu Neg Metastatic Breast Cancer

A Phase II Study of Carboplatin and Bevacizumab (Avastin) Combination Therapy for ER Negative, PR Negative, and HER2/Neu Negative Metastatic Breast Cancer

The purpose of this study is to determine the progression free survival (PFS) of metastatic ER, PR and HER2/neu negative breast cancers to the combination of carboplatin and bevacizumab (Avastin®) therapy.

Study Overview

• Status: Terminated
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: carboplatin; Drug: bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Park Ridge, Illinois, United States, 60068
      • Oncology Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have pathologically confirmed ER, PR and HER2/neu negative (FISH ratio of <2.0 or IHC <1+) metastatic breast cancer. Locally advanced or recurrent disease is also eligible.
• Patients must have measurable disease
• Patients must not have received prior chemotherapy for metastatic breast cancer (not including adjuvant therapy). Patients should be > 4 weeks from their most recent chemotherapy or radiation therapy treatment.
• Age >18 years
• ECOG performance status <1 (Karnofsky >80%).
• Patients must have normal organ and marrow function as defined below:
• absolute neutrophil count >1,500/uL
• platelets >100,000/uL
• total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) <2.5X institutional upper limit of normal
• creatinine within normal institutional limits OR creatinine clearance>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• PT INR < 1.5 (Unless patient is on anticoagulation)
• urine protein <1+
• Tissue from the primary tumor must be available for correlative studies
• Women of child-bearing potential must agree to use adequate contraception
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients who have had prior therapy with platinum agents or a VEGF inhibitor are not eligible.
• Patients may not be receiving any other investigational agents.
• Patients with known brain metastases will be excluded
• Patients may have had prior radiation therapy, provided the patient has measurable disease and there has been clear progression since the completion of radiation therapy. Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to therapy administered more than 4 weeks earlier will be excluded.
• Patients with significant cardiac dysfunction will be excluded
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study, breastfeeding should be discontinued.
• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with carboplatin or the other agents administered during the study.
• Patients with evidence of bleeding diathesis or coagulopathy.
• Patients with inadequately controlled hypertension will be excluded
• Patients who have had a stroke or TIA within 6 months of registration will be excluded.
• Patients with a history of hypertensive crisis or hypertensive encephalopathy will be excluded.
• Patients with a history of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months of registration.
• Patient with history of serious non-healing wound, ulcer or bone fracture.
• Patients with major surgery, open biopsy, or significant traumatic injury within 28 days of registration or anticipated need for surgery during course of study treatment.
• Patients with a history core biopsy or other minor surgery, excluding venous access device (VAD) placement, within 7 days of registration.
• Patients with active second malignancy.
• Known hypersensitivity to any component of bevacizumab (Avastin®).
• Peripheral neuropathy > Grade 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carboplatin + Avastin	Drug: carboplatin; AUC 6 in 250mL saline IV over 30 minutes; Drug: bevacizumab; 15mg/kg in 100mL saline IV over 60 - 90 minutes; Other Names: Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Progression is defined using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000], as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions, or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Response is defined using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000]: Complete Response (CR), Disappearance of all target lesions or disappearance of all non-target lesions and normalization of tumor marker level; Partial Response (PR), At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started, or persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.	Up to 5 years
Duration of Response		Up to 5 years
Correlation of Response to BRCA1 Methylation Status	The methylation status of the tumor is defined using Methylation Specific polymerase chain reaction and/or pyrosequencing.	Up to 5 years

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: August 14, 2007
• First Submitted That Met QC Criteria: August 14, 2007
• First Posted (Estimate): August 16, 2007

Study Record Updates

• Last Update Posted (Estimate): April 15, 2014
• Last Update Submitted That Met QC Criteria: March 10, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Carboplatin; Bevacizumab
• Other Study ID Numbers: 15578A