Vaccine Therapy, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

NCT01222221 | Completed Phase 1

• 3 other identifiers: CDR0000686559CRUK-CR0902-11EUDRACT-2009-015971-28
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 7

Brief Summary

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving vaccine therapy together with temozolomide and radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects of vaccine therapy when given together with temozolomide and radiation therapy in treating patients with newly diagnosed glioblastoma multiforme.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult gliosarcoma; adult giant cell glioblastoma; adult glioblastoma

Outcome Measures

Primary Outcomes (2)

• Causality of each adverse event (AE) to glioblastoma multiform multi-antigen vaccine IMA950 and GM-CSF and AE severity according to NCI CTCAE Version 4.0

• Total number of patients showing patient-individual T-cell responses against a single or multiple tumor-associated peptides (TUMAP) contained in the study vaccine IMA950 at one or more post-vaccination time points by HLA multimer analysis

Secondary Outcomes (4)

• Progression-free survival (PSF) at 6 and 9 months post-surgery as assessed by the Macdonald criteria from conventional gadolinium-enhanced MRI and clinical assessment

• Correlation between steroid levels and observed T-cell responses

• Correlation between O6-methyl-DNA-methyltransferase (MGMT) promoter methylation status in tumor tissue using methylation-specific polymerase chain reaction and clinical benefit (PFS at 6 months and 9 months)

• Kinetics of vaccine-induced TUMAP responses including summary descriptions of the time of onset, sustainability, and magnitude of the observed response

Interventions

glioblastoma multiforme multipeptide vaccine IMA950 BIOLOGICAL

sargramostim BIOLOGICAL

temozolomide DRUG

laboratory biomarker analysis OTHER

pharmacological study OTHER

adjuvant therapy PROCEDURE

radiation therapy RADIATION

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed glioblastoma multiforme (astrocytoma WHO grade IV disease) * Newly diagnosed disease * Resectable tumor (not including patients undergoing biopsy only or tumors involving the brain stem or cerebellum) * Meets 1 of the following criteria regarding standard chemoradiotherapy: * Cohort 1 * Eligible for standard chemoradiotherapy with temozolomide followed by adjuvant temozolomide * Has undergone surgical resection before study enrollment * Cohort 2 * Completed standard chemoradiotherapy with temozolomide with no subsequent progression of disease * Expected to complete standard chemoradiotherapy and 6 courses of adjuvant temozolomide * HLA-A\*02 positive PATIENT CHARACTERISTICS: * WHO performance status 0-1 * Life expectancy ≥ 30 weeks * Hemoglobin ≥ 9.0 g/dL * Absolute neutrophil count ≥ 1.5 x 10\^9/L * Lymphocyte count ≥ 1.0 x 10\^9/L (cohort 1) OR ≥ 0.35 x 10\^9/L post-chemoradiotherapy and ≥ 1.0 x 10\^9/L prior to the start of chemoradiotherapy (cohort 2) * Serum bilirubin ≤ 1.5 times upper limit of normal (ULN) * ALT or AST ≤ 3.0 times ULN * Alkaline phosphatase ≤ 3.0 times ULN * Hepatitis B serology negative (HBcAg-seronegative) * No known hepatitis C or HIV serological positivity * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use one (male) or two (female) highly effective forms of contraception 2 weeks before, during, and for 6 months after completion of study therapy * Not at high medical risk due to nonmalignant systemic disease including active uncontrolled infection * No known hypersensitivity to GM-CSF or excipients * No history of autoimmune disease * No concurrent congestive heart failure * No prior history of NYHA class III-IV cardiac disease, cardiac ischemia, or cardiac arrhythmia * No other condition that might interfere with the patient's ability to generate an immune response * No other condition that, in the investigator's opinion, would make the patient not a good candidate for the clinical trial PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 7 days since prior dexamethasone (dose \> 4 mg daily or equivalent) * At least 4 weeks since prior major surgery for any condition (except surgical resection as part of primary standard therapy in cohort 1) * At least 30 days since prior and no concurrent participation in another clinical trial or planning to participate in another interventional clinical trial (concurrent participation on an observational study allowed) * At least 30 days since prior and no other concurrent investigational drugs * No prior treatment for glioblastoma including Gliadel Wafers * Early components of standard therapy are allowed if already initiated (i.e., surgical resection \[cohort 1\] or surgical resection followed by conventional external-beam radiotherapy and concomitant temozolomide \[cohort 2\]) * No other concurrent anticancer therapy * No other concurrent vaccinations from 2 weeks before the first study vaccine to the end of the sixth study vaccine (the induction phase)

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

Sponsors & Collaborators

• Cancer Research UK: lead
• Immatics Biotechnologies GmbH: collaborator

Study Sites (7)

Addenbrooke's Hospital

Cambridge, England, CB2 2QQ, United Kingdom

Location

UCL Cancer Institute

London, England, WC1E 6DD, United Kingdom

Location

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, G12 0YN, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

St James' University Hospital

Leeds, LS9 7TF, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Gliosarcoma; Glioblastoma

Interventions

IMA950; sargramostim; Temozolomide; Chemotherapy, Adjuvant; Radiotherapy

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Roy Rampling, MD, PhD

  University of Glasgow

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2010
• First Posted: October 18, 2010
• Study Start: July 1, 2010
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: October 14, 2015

Record last verified: 2015-10

Locations

GB (7)