Vaccine Therapy With Bevacizumab Versus Bevacizumab Alone in Treating Patients With Recurrent Glioblastoma Multiforme That Can Be Removed by Surgery
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01814813|
Recruitment Status : Active, not recruiting
First Posted : March 20, 2013
Results First Posted : June 12, 2019
Last Update Posted : July 24, 2020
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Glioblastoma Recurrent Adult Brain Tumor Gliosarcoma||Biological: HSPPC-96 Drug: bevacizumab||Phase 2|
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:
- to evaluate the safety and tolerability of HSPPC-96 with bevacizumab
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||90 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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)|
|Study Start Date :||May 2013|
|Actual Primary Completion Date :||April 3, 2017|
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. HSPPC-96 should be administered at least 60 minutes prior to starting bevacizumab infusion. (1 cycle=14 days)
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.
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.
Upon confirmation of progression the patient should initiate bevacizumab within 7-42 days from the last dose of vaccine.
Active Comparator: Arm 3, Bevacizumab
Bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until progression. (1 cycle = 14 days)
- Overall Survival (OS) [ Time Frame: Up to 5 years post-surgery ]The primary endpoint is overall survival (OS), which is defined as the date from study> registration to the date of death, due to any cause.
- Progression Free Survival (PFS) [ Time Frame: Up to 5 years post-surgery ]Time to progression free survival: which is defined as the date from study registration to the date of first observation of disease progression or death due to any cause (whichever comes first). Progressive disease is defined as one or more of the following:New contrast-enhancing lesion outside of radiation field on decreasing, stable, or increasing doses of corticosteroids, increase by > 50% enhancement from the first post-surgical scan, or a subsequent scan with smaller tumor size, and the scan 8 weeks or later on stable or increasing doses of corticosteroids, clinical deterioration not attributable to concurrent medication or comorbid conditions is sufficient to declare progression on current treatment, for patients receiving bevacizumab therapy, significant increase in T2/FLAIR non-enhancing lesion.
- Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (v5) [ Time Frame: Up to 3 years ]The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01814813
|Study Chair:||Ian Parney, MD, PhD||Mayo Clinic|
|Study Chair:||Orin Bloch, MD||Northwestern University|