Trial record 1 of 1 for:    NCT 01814813
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Vaccine Therapy With Bevacizumab Versus Bevacizumab Alone in Treating Patients With Recurrent Glioblastoma Multiforme That Can Be Removed by Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Alliance for Clinical Trials in Oncology
Sponsor:
Collaborators:
Agenus, Inc.
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01814813
First received: March 18, 2013
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Biological: HSPPC-96
Drug: bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Overall survival (OS) [ Time Frame: Up to 6.5 years post surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Up to 6.5 years post surgery ] [ Designated as safety issue: No ]
  • Treatment related adverse events graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 222
Study Start Date: May 2013
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1, HSPPC-96 + concomitant bevacizumab

HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles), plus bevacizumab 10 mg/kg intravenous (IV) on day 1 of each cycle, until progression. (1 cycle=14 days) HSPPC-96 should be administered at least 60 minutes prior to starting bevacizumab infusion.

Note: If HSPPC-96 treatment has ended but there is no evidence of disease progression, the patient should continue to receive bevacizumab at the specified dose until progression.

Biological: HSPPC-96
intradermal administration
Drug: bevacizumab
intravenous infusion
Experimental: Arm 2, HSPPC-96 with bevacizumab at progression

HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles). At progression: bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until further progression. (1 cycle = 14 days)

NOTE: It is possible that HSPPC-96 vaccination may end prior to evidence of progression. In this instance it is important to wait until there is confirmed evidence of progression before initiating treatment with bevacizumab.

Biological: HSPPC-96
intradermal administration
Drug: bevacizumab
intravenous infusion
Active Comparator: Arm 3, Bevacizumab
Bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until progression. (1 cycle = 14 days)
Drug: bevacizumab
intravenous infusion

Detailed Description:

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. Upon confirmation of adequacy of tissue for vaccine manufacture and ≥ 90% resection by central radiology review, patients will be randomized to one of three treatment arms. Please see the "Arms" section for more details.

Patients will be monitored approximately 6.5 years post surgery.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Pre-registration (Pre-Surgery) Eligibility Criteria

  • Histologic documentation: Prior histologic diagnosis of GBM at first occurrence.
  • Stage: First or second recurrence of GBM 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
  • ≥ 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).
  • ≥ 9 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
  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: NCT01814813

  Show 34 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Agenus, Inc.
Investigators
Study Chair: Andrew Parsa, M.D., Ph.D. University of California at San Francisco
  More Information

No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT01814813     History of Changes
Other Study ID Numbers: A071101, U10CA031946, NCI-2013-00444
Study First Received: March 18, 2013
Last Updated: April 10, 2014
Health Authority: United States: Food and Drug Administration
United States: NCI Central Institutional Review Board

Additional relevant MeSH terms:
Brain Neoplasms
Glioblastoma
Gliosarcoma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2014