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Eligibility
for people ages 18 years and up
Location
at San Francisco, California and other locations
Dates
study started

Description

Summary

This randomized phase II trial studies how well giving vaccine therapy with or without bevacizumab works in treating patients with recurrent glioblastoma multiforme that can be removed by surgery. Vaccines consisting of heat shock protein-peptide complexes made from a person's own tumor tissue may help the body build an effective immune response to kill tumor cells that may remain after surgery. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them. It is not yet known whether giving vaccine therapy is more effective with or without bevacizumab in treating glioblastoma multiforme.

Official Title

A Phase II Randomized Trial Comparing the Efficacy of Heat Shock Protein-Peptide Complex-96 (HSPPC-96) (NSC #725085, ALLIANCE IND # 15380) Vaccine Given With Bevacizumab Versus Bevacizumab Alone in the Treatment of Surgically Resectable Recurrent Glioblastoma Multiforme (GBM)

Details

The purpose of this study is to compare the effects of a vaccine with bevacizumab versus bevacizumab alone on a patient's brain tumor. The vaccine is called heat shock protein peptide complex 96 (HSPPC-96). HSPPC-96 is experimental. Specifically, HSPPC-96 is a protein that may work to help the body have a response against remaining brain tumor cells. Bevacizumab has been approved by the Food and Drug administration for treating brain tumors that grow back. In this study, patients will either get HSPPC-96 vaccine at the same time as bevacizumab, HSPPC vaccine first and then bevacizumab if the tumor comes back, or bevacizumab alone. The use of HSPPC-96 and bevacizumab is investigational.

The primary objective of the study is to determine whether there is an overall survival advantage of HSPPC-96 administered with bevacizumab, given concomitantly or at the point of progression, in comparison with bevacizumab alone in patients with surgically resectable recurrent glioblastoma multiforme.

The secondary objectives are:

  1. to evaluate the safety and tolerability of HSPPC-96 with bevacizumab
  2. to evaluate the progression free survival of HSPPC-96 with bevacizumab, given concomitantly or at the point of progression.

Patients must undergo surgery within 28 days from pre-registration. There must be confirmation of adequacy of tissue for vaccine manufacture, tumor tissue submitted to Agenus, confirmation of ≥ 90% resection by central radiology review and vaccine manufacture of at least six vials. Patients will be randomized to one of three treatment arms. Please see the "Arms" section for more details.

Patients will be monitored approximately 5 years post-surgery.

Keywords

Recurrent Glioblastoma Recurrent Adult Brain Tumor Gliosarcoma Vaccines Bevacizumab

Eligibility

For people ages 18 years and up

Pre-registration (Pre-Surgery) Eligibility Criteria

  • Histologic documentation: Prior histologic diagnosis of GBM at first occurrence
  • Stage: First or second recurrence of GBM or gliosarcoma considered to be surgically resectable
  • Prior Treatment:
  • No radiotherapy within 90 days prior to pre-registration
  • No prior treatment with any anti-angiogenic agent targeting the VEGF pathway including but not limited to bevacizumab, cediranib, vandetanib, sunitinib,pazopanib, aflibercept, or sorafenib
  • No prior treatment with HSPPC-96 or other investigational immunotherapy
  • Must have received prior treatment with radiotherapy and temozolomide for histologically confirmed GBM at initial diagnosis
  • No tumor directed therapy for most recent progression
  • No prior Gliadel® wafers
  • No clinically significant cardiovascular disease:
  • Patients with a history of hypertension must be well controlled (<150/90) on a regimen of antihypertensive therapy.
  • History of arterial thrombotic events within the past 6 months, including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medial intervention in the past 6 months, or myocardial infarction (MI). Patients with clinically significant peripheral artery disease (i.e., claudication on less than one block), significant vascular disease (i.e., aortic aneurysm, history of aortic dissection) are not eligible.
  • Patients who have had a deep vein thrombosis or pulmonary embolus within the past 6 months are eligible if they are on stable therapeutic anticoagulation
  • No current New York Heart Association classification II, III or IV congestive heart failure
  • No significant bleeding within the past 6 months; no bleeding diathesis or coagulopathy
  • No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within past 12 months
  • No evidence of any systemic autoimmune disease (e.g. Hashimoto's thyroiditis) and/or any history of primary or secondary immunodeficiency, and no immunosuppressant therapy (with the exception of dexamethasone as noted below) for any reason
  • Age ≥ 18 years of age
  • Karnofsky functional status rating ≥70
  • No more than 16 mg dexamethasone (or equivalent) per day
  • Non-pregnant and non-nursing

    Registration (Post-Surgery) Eligibility Criteria

  • Pre-registration eligibility criteria continue to be met
  • Histologic documentation: confirmed histological diagnosis of recurrent GBM or gliosarcoma
  • ≥ 90% surgical resection of recurrent GBM confirmed by central radiology review by MRI with or without gadolinium per institutional guidelines. A CT scan is allowable in place of MRI only in situations where an MRI is contraindicated (e.g., patient has a heart pacemaker, metallic devices in the eye, brain or spine, severe claustrophobia).
  • ≥ 7 grams of resected tumor available for vaccine manufacture as determined by institutional pathologist
  • Availability of ≥ 6 clinical vials of HSPPC-96
  • Required Initial Laboratory Values:
  • Granulocytes ≥1,500/µL
  • Platelet count ≥100,000/µL
  • Total Bilirubin ≤ 2.0 x ULN
  • UPC ratio <1 or Urine protein ≤ 1+
  • Calculated creatinine clearance ≥ 45 ml/min
  • SGOT/SGPT(AST/ALT) ≤ 2.5 x ULN
  • No serious, non-healing wounds or ulcers
  • At least 7 days since any minor surgery such as port placement
  • No major surgical procedures, open biopsy or significant traumatic injury ≤ 28 days prior to registration or anticipation of need for elective or planned major surgical procedure during the study. Core biopsy or other minor surgical procedures ≤7 days prior to registration.
  • No active or recent hemoptysis (≥½ teaspoon of bright red blood per episode) ≤ 30 days prior to registration
  • No new bleeding on D28 (+/-3) MRI (or CT if MRI is contraindicated)
  • No clinical deterioration at the time of registration/randomization
  • If a second surgery is needed for completion of resection, this should be within 30 days from the first surgery

Locations

  • California Pacific Medical Center-Pacific Campus
    San Francisco, California, 94115, United States
  • Kaiser Permanente-San Francisco
    San Francisco, California, 94115, United States
  • Fresno Cancer Center
    Fresno, California, 93720, United States
  • Kaiser Permanente
    Fresno, California, 93720, United States
  • Kaiser Permanente Cancer Treatment Center
    South San Francisco, California, 94080, United States
  • Kaiser Permanente-South San Francisco
    South San Francisco, California, 94080, United States
  • Bay Area Breast Surgeons Inc
    Emeryville, California, 94608, United States
  • Epic Care Partners in Cancer Care
    Emeryville, California, 94608, United States
  • Alta Bates Summit Medical Center - Summit Campus
    Oakland, California, 94609, United States
  • Bay Area Tumor Institute
    Oakland, California, 94609, United States
  • Alta Bates Summit Medical Center-Herrick Campus
    Berkeley, California, 94704, United States
  • Kaiser Permanente-Richmond
    Richmond, California, 94801, United States
  • Mills - Peninsula Hospitals
    Burlingame, California, 94010, United States
  • Kaiser Permanente Oakland-Broadway
    Oakland, California, 94611, United States
  • Kaiser Permanente-Oakland
    Oakland, California, 94611, United States
  • Kaiser Permanente San Leandro
    San Leandro, California, 94577, United States
  • Kaiser Permanente-San Rafael
    San Rafael, California, 94903, United States
  • Eden Hospital Medical Center
    Castro Valley, California, 94546, United States
  • Contra Costa Regional Medical Center
    Martinez, California, 94553-3156, United States
  • Kaiser Permanente-Redwood City
    Redwood City, California, 94063, United States
  • Kaiser Permanente-Walnut Creek
    Walnut Creek, California, 94596, United States
  • Palo Alto Medical Foundation Health Care
    Palo Alto, California, 94301, United States
  • Stanford Cancer Institute
    Palo Alto, California, 94304, United States
  • Kaiser Permanente-Vallejo
    Vallejo, California, 94589, United States
  • Sutter Solano Medical Center/Cancer Center
    Vallejo, California, 94589, United States
  • Epic Care-Dublin
    Dublin, California, 94568, United States
  • Kaiser Permanente-Fremont
    Fremont, California, 94538, United States
  • Palo Alto Medical Foundation-Camino Division
    Mountain View, California, 94040, United States
  • Palo Alto Medical Foundation-Gynecologic Oncology
    Mountain View, California, 94040, United States
  • Palo Alto Medical Foundation-Sunnyvale
    Sunnyvale, California, 94086, United States
  • Kaiser Permanente Medical Center - Santa Clara
    Santa Clara, California, 95051, United States
  • Kaiser Permanente-Deer Valley Medical Center
    Antioch, California, 94531, United States
  • Rohnert Park Cancer Center
    Rohnert Park, California, 94928, United States
  • Sutter Cancer Centers Radiation Oncology Services-Vacaville
    Vacaville, California, 95687, United States
  • Kaiser Permanente Medical Center-Vacaville
    Vacaville, California, 95688, United States
  • Kaiser Permanente-Santa Teresa-San Jose
    San Jose, California, 95119, United States
  • Kaiser Permanente-Santa Rosa
    Santa Rosa, California, 95403, United States
  • Sutter Pacific Medical Foundation
    Santa Rosa, California, 95403, United States
  • Palo Alto Medical Foundation-Santa Cruz
    Santa Cruz, California, 95065, United States
  • Kaiser Permanente-Stockton
    Stockton, California, 95210, United States
  • Sutter Davis Hospital
    Davis, California, 95616, United States
  • Kaiser Permanente-South Sacramento
    Sacramento, California, 95823, United States
  • South Sacramento Cancer Center
    Sacramento, California, 95823, United States
  • Sutter General Hospital
    Sacramento, California, 95816, United States
  • Kaiser Permanente-Modesto
    Modesto, California, 95356, United States
  • Kaiser Permanente - Sacramento
    Sacramento, California, 95825, United States
  • Memorial Medical Center
    Modesto, California, 95355, United States
  • Kaiser Permanente-Rancho Cordova Cancer Center
    Rancho Cordova, California, 95670, United States
  • The Permanente Medical Group-Roseville Radiation Oncology
    Roseville, California, 95678, United States
  • Kaiser Permanente-Roseville
    Roseville, California, 95661, United States
  • Sutter Cancer Centers Radiation Oncology Services-Roseville
    Roseville, California, 95661, United States
  • Sutter Roseville Medical Center
    Roseville, California, 95661, United States
  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    Cameron Park, California, 95682, United States
  • Sutter Cancer Centers Radiation Oncology Services-Auburn
    Auburn, California, 95603, United States
  • Sutter Auburn Faith Hospital
    Auburn, California, 95602, United States
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    Burbank, California, 91505, United States
  • Kaiser Permanente Los Angeles Medical Center
    Los Angeles, California, 90027, United States

Details

Status
in progress, not accepting new patients
Start Date
Sponsor
Alliance for Clinical Trials in Oncology
ID
NCT01814813
Phase
Phase 2
Study Type
Interventional
Last Updated
March 1, 2017