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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Immatics Biotechnologies Ltd
Information provided by (Responsible Party):
Cancer Research UK
ClinicalTrials.gov Identifier:
NCT01222221
First received: October 14, 2010
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Biological: glioblastoma multiforme multipeptide vaccine IMA950
Biological: sargramostim
Drug: temozolomide
Other: laboratory biomarker analysis
Other: pharmacological study
Procedure: adjuvant therapy
Radiation: radiation therapy
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Cancer Research UK Phase I Trial of IMA950 (A Novel Multi-Peptide Vaccine) Plus GM-CSF in Patients With Newly Diagnosed Glioblastoma

Resource links provided by NLM:


Further study details as provided by Cancer Research UK:

Primary Outcome Measures:
  • 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 [ Designated as safety issue: Yes ]
  • 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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Designated as safety issue: No ]
  • Correlation between steroid levels and observed T-cell responses [ Designated as safety issue: No ]
  • 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) [ Designated as safety issue: No ]
  • Kinetics of vaccine-induced TUMAP responses including summary descriptions of the time of onset, sustainability, and magnitude of the observed response [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: July 2010
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

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

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)
  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: NCT01222221

Locations
United Kingdom
Addenbrooke's Hospital
Cambridge, England, United Kingdom, CB2 2QQ
UCL Cancer Institute
London, England, United Kingdom, WC1E 6DD
Southampton General Hospital
Southampton, England, United Kingdom, SO16 6YD
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, United Kingdom, G12 0YN
Western General Hospital
Edinburgh, United Kingdom, EH4 2XU
St James' University Hospital
Leeds, United Kingdom, LS9 7TF
The Christie NHS Foundation Trust
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Cancer Research UK
Immatics Biotechnologies Ltd
Investigators
Principal Investigator: Roy Rampling, MD, PhD University of Glasgow
  More Information

Additional Information:
No publications provided

Responsible Party: Cancer Research UK
ClinicalTrials.gov Identifier: NCT01222221     History of Changes
Other Study ID Numbers: CDR0000686559, CRUK-CR0902-11, EUDRACT-2009-015971-28
Study First Received: October 14, 2010
Last Updated: July 22, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Cancer Research UK:
adult gliosarcoma
adult giant cell glioblastoma
adult glioblastoma

Additional relevant MeSH terms:
Glioblastoma
Central Nervous System Neoplasms
Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Nervous System Diseases
Neuroectodermal Tumors
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014