NCT01814813|TerminatedPhase 2ResultsDMC

Study Stopped

DSMB futility analysis

Vaccine Therapy With Bevacizumab Versus Bevacizumab Alone in Treating Patients With Recurrent Glioblastoma Multiforme That Can Be Removed by Surgery

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)

Alliance for Clinical Trials in Oncology ClinicalTrials.gov

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3 other identifiers

A071101U10CA031946NCI-2013-00444

Study Type

interventional

Target

Locations

1 country

Sites

417

Timeline

RegisteredMar 2013

StartedJun 2013

CompletionMay 2023

Brief 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.

Trial Health

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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P50-P75 for phase_2

Timeline

Completed

Started Jun 2013

Longer than P75 for phase_2

Geographic Reach

1 country

417 active sites

Status

terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

9.9 years study duration

First Submitted

Initial submission to the registry

March 18, 2013

Completed

2 days until next milestone

First Posted

Study publicly available on registry

March 20, 2013

Completed

3 months until next milestone

Study Start

First participant enrolled

June 19, 2013

Completed

3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 3, 2017

Completed

2.2 years until next milestone

Results Posted

Study results publicly available

June 12, 2019

Completed

3.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 22, 2023

Completed

Last Updated

January 24, 2025

Status Verified

January 1, 2025

Enrollment Period

3.8 years

First QC Date

March 18, 2013

Results QC Date

April 8, 2019

Last Update Submit

January 13, 2025

Conditions

Recurrent Glioblastoma Recurrent Adult Brain Tumor Gliosarcoma

Outcome Measures

Primary Outcomes (1)

Overall Survival (OS)
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.
Up to 5 years post-surgery

Secondary Outcomes (2)

Progression Free Survival (PFS)
Up to 5 years post-surgery
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (v5)
Up to 3 years

Study Arms (3)

Arm 1, HSPPC-96 + concomitant bevacizumab

EXPERIMENTAL

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.

Biological: HSPPC-96Drug: bevacizumab

Arm 2, HSPPC-96 with bevacizumab at progression

EXPERIMENTAL

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.

Biological: HSPPC-96Drug: bevacizumab

Arm 3, Bevacizumab

ACTIVE COMPARATOR

Bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until progression. (1 cycle = 14 days)

Drug: bevacizumab

Interventions

HSPPC-96BIOLOGICAL

intradermal infusion

Arm 1, HSPPC-96 + concomitant bevacizumabArm 2, HSPPC-96 with bevacizumab at progression

bevacizumabDRUG

intravenous

Arm 1, HSPPC-96 + concomitant bevacizumabArm 2, HSPPC-96 with bevacizumab at progressionArm 3, Bevacizumab

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Alliance for Clinical Trials in Oncologylead
National Cancer Institute (NCI)collaborator
Agenus Inc.collaborator

Study Sites (417)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC