Bevacizumab in Pats w/ Recurrent ST Brain Metas Who Have Failed Whole Brain Radiation Therapy

NCT ID: NCT01898130

Last Updated: 2019-09-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-27
• Study Completion Date: 2018-09-05

Brief Summary

This is a study to evaluate a drug called bevacizumab in patients with cancer whose disease has spread to their brain. This study will not evaluate the effect of bevacizumab on the systemic solid tumor cancer. Bevacizumab is a medication and it is thought that bevacizumab may interfere with the growth of new blood vessels; therefore it might stop tumor growth and possibly shrink the tumor by keeping it from receiving nutrients and oxygen supplied by the blood vessels.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the radiographic response rate in patients with solid tumor brain metastases treated with bevacizumab.

SECONDARY OBJECTIVES:

I. Estimate the progression-free survival (PFS) rate at 6 months. II. Determine the time to progression based on magnetic resonance imaging (MRI) or computed tomography (CT) scans.

III. Determine the time to response based on radiographic imaging. IV. Determine the duration of response based on radiographic imaging. V. Determine overall survival. VI. Collect additional safety data. VII. Assess changes in quality of life using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) while on treatment.

OUTLINE:

Patients receive bevacizumab intravenously (IV) over 30-90 minutes every 2 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 8 weeks.

Conditions

Metastatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (bevacizumab)

Patients receive bevacizumab IV over 30-90 minutes every 2 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

bevacizumab

Intervention Type: BIOLOGICAL

Given IV

quality-of-life assessment

Intervention Type: PROCEDURE

Ancillary studies

Interventions

bevacizumab

Given IV

Intervention Type: BIOLOGICAL

quality-of-life assessment

Ancillary studies

Intervention Type: PROCEDURE

Other Intervention Names

anti-VEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; Avastin; rhuMAb VEGF; quality of life assessment

Eligibility Criteria

Inclusion Criteria

• Patients must have a histologically or cytologically confirmed non-central nervous system (CNS) primary solid malignancy at the time of initial diagnosis; NOTE: brain lesions are not required to have pathologic confirmation; in addition, a copy of the pathology report for the primary tumor is sufficient for registration purposes
• Patients must have radiographically-confirmed recurrent brain metastases from a solid tumor after WBRT
• Patients must have measurable or evaluable disease in the brain
• Patients must have been on a stable dose of corticosteroids >= 5 days prior to obtaining their baseline gadolinium (Gd)-MRI of brain
• Patients must have completed WBRT > 12 weeks prior to enrollment to limit cases of pseudoprogression; however if new lesions are noted < 12 weeks but > 4 weeks prior to enrollment, those patients are eligible
• Patients who underwent radiosurgery to treat a progressive lesion must have confirmation of tumor by tissue, magnetic resonance spectroscopy (MRS), magnetic resonance (MR) perfusion or positron emission tomography (PET) and the lesion must be measurable; NOTE: radiosurgery may be done to a lesion that will not be used for response evaluation and should be done > 2 weeks prior to enrollment
• Patients may be on other systemic chemotherapies if progressive CNS disease occurs while on these treatments; NOTE: new systemic chemotherapies should not be started unless required to treat systemic disease and should not start until at least 1 follow up imaging study has been performed
• Patients may have received any number of prior CNS directed therapies - there are no limitations
• Patients must have a life expectancy of >= 12 weeks
• Patients must have a Karnofsky performance score (KPS) of >= 60
• Whole blood cell (WBC) >= 3,000/ul
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelets >= 100,000/mm^3
• Hemoglobin >= 10 gm/dl (may be reached by transfusion)
• Serum glutamic oxaloacetic transaminase (SGOT) < 2 x upper limit of normal (ULN) (or < 5 x ULN if liver is involved)
• Bilirubin < 2 x ULN (or < 5 x ULN if liver is involved)
• Creatinine < 1.5 x ULN
• Patients of both sexes must agree to the use of barrier contraceptives throughout the duration of treatment on this trial and for 3 months after discontinuing treatment; NOTE: hormonal contraceptives are not acceptable as a sole method of contraception
• Patients must be > 4 weeks from any major surgery
• Patients NOT on warfarin must have a prothrombin time (PT)/international normalized ratio (INR) < 1.4 within 14 days prior to registration

• Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight [LMW] heparin) must meet BOTH of the following criteria within 14 days prior to registration:

• No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
• In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of LMW heparin
• Female patients of child-bearing potential must have a negative pregnancy test within 14 days prior to registration
• Patients must be willing and able to comply with study and/or follow-up procedures
• Patients must sign an informed consent prior to registration and before undergoing any study-specific procedures indicating that they are aware of the investigational nature of this study

Exclusion Criteria

• Patients with a diagnosis of intrathoracic lung carcinoma of squamous cell histology are not eligible for participation
• Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using barrier birth control methods, are not eligible for participation
• Patients must not have baseline proteinuria within 14 days prior to registration as demonstrated by either:

• Urine protein: creatinine (UPC) ratio < 1.0 at screening, OR
• Urine dipstick for proteinuria =< 2+; NOTE: patients discovered to have >= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate =< 1g of protein in 24 hours to be eligible
• Patients must not have experienced any major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, or be anticipated to need a major surgical procedure during the course of the study; NOTE: the exception is craniotomy
• Patients must not have experienced a core biopsy or other minor surgical procedure within 7 days prior to registration; NOTE: this excludes placement of a vascular access device
• Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the previous 6 months are not eligible for participation
• Patients with a serious, non-healing wound, ulcer, or bone fracture are not eligible for participation due to the effects on vasculature by bevacizumab which may impair healing
• Patients known to be human immunodeficiency virus (HIV) or hepatitis B and/or C positive are not eligible for participation; NOTE: HIV and hepatitis testing is not required for study participation
• Patients with a history of any other cancer (except for non-melanoma skin cancer or carcinoma in-situ of the cervix), are not eligible for participation unless they are in complete remission and have been off of all therapy for that disease for a minimum of 3 years
• Patients receiving or participating on any other experimental agents/clinical trials are not eligible for participation
• Patients with a known hypersensitivity to any component of bevacizumab are not eligible for participation
• Patients with any significant medical illnesses or infection that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy are not eligible for participation
• Patients with leptomeningeal disease are not eligible for participation
• Patients who have received previous treatment with bevacizumab for CNS disease are not eligible for participation
• Patients with inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg) are not eligible for participation

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Priya Kumthekar

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Northwestern University

Chicago, Illinois, United States

Northwestern Memorial Hospital: Lake Forest Hospital

Lake Forest, Illinois, United States

Cadence Health - CDH

Warrenville, Illinois, United States

Columbia University Medical Center

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2013-00448

Identifier Type: REGISTRY

Identifier Source: secondary_id

STU00080404

Identifier Type: OTHER

Identifier Source: secondary_id

NU 12C06

Identifier Type: -

Identifier Source: org_study_id