Brain and Central Nervous System TumorsPhase 1NCT01222221
Vaccine Therapy, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
A Phase 1 study testing glioblastoma multiforme multipeptide vaccine IMA950, sargramostim and temozolomide in people with Brain and Central Nervous System Tumors, run by Cancer Research UK at 7 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- glioblastoma multiforme multipeptide vaccine IMA950, sargramostim and temozolomide
- Type of treatment
- Vaccines, Surgery or procedure
- How many people
- 45 participants
- Where
- 7 sitesUnited Kingdom
- Study dates
- Jul 2010to Feb 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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)
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United Kingdom7 sites
Addenbrooke's Hospital
Cambridge, England, CB2 2QQ
Western General Hospital
Edinburgh, EH4 2XU
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, G12 0YN
St James' University Hospital
Leeds, LS9 7TF
UCL Cancer Institute
London, England, WC1E 6DD
The Christie NHS Foundation Trust
Manchester, M20 4BX
Southampton General Hospital
Southampton, England, SO16 6YD
About this study
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
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.
Read the detailed description
OBJECTIVES:
Primary
- To assess the safety and tolerability of glioblastoma multiform multi-antigen vaccine IMA950 plus sargramostim (GM-CSF) in combination with standard chemoradiotherapy comprising temozolomide and radiotherapy followed by adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme.
- To determine the immunogenicity of this regimen in these patients.
Secondary
- To determine the anti-tumor effect of this regimen in these patients.
- To determine the effect of pre-treatment levels of regulatory T-cells on the immunogenicity of this regimen in these patients. (Exploratory)
- To evaluate the potential effect of steroid dose on the immunological response to glioblastoma multiform multi-antigen vaccine IMA950 plus GM-CSF.
Tertiary
- To assess the level of O6-methyl-DNA-methyltransferase (MGMT) promoter methylation in tumor tissue and any potential association with any observed anti-tumor effect.
- To evaluate the kinetics of the observed immunogenicity of glioblastoma multiform multi-antigen vaccine IMA950 plus GM-CSF.
- To explore the possible biomarker signatures that may predict immunological response to glioblastoma multiform multi-antigen vaccine IMA950 plus GM-CSF. (Exploratory)
- To explore the possible effects of this regimen on any observed pseudo-progression and pseudo-regression in these patients. (exploratory)
OUTLINE: This is a multicenter study. Patients are recruited to cohort 1 or 2 with priority recruitment to cohort 1. All patients undergo standard chemoradiotherapy followed by adjuvant temozolomide as planned.
- Standard therapy (chemoradiotherapy and adjuvant temozolomide): Beginning after surgery, patients receive chemoradiotherapy comprising oral temozolomide daily for 6 weeks and radiotherapy once daily, 5 days a week for 6 weeks. Beginning 35 days after completion of radiotherapy, patients receive adjuvant oral temozolomide alone on days 1-5. Treatment with temozolomide repeats every 28 days for 6 courses.
- Vaccine therapy: Patients also receive vaccine therapy beginning at one of two time points. Patients are recruited into 1 of 2 cohorts that differ in the timing of the vaccination schedule in relation to a patient's standard therapy.
- Cohort 1: Vaccination begins 7-14 days prior to chemoradiotherapy.
- Induction phase: Patients receive the first 6 doses of sargramostim intradermally (ID) followed by glioblastoma multiform multi-antigen vaccine IMA950 ID on days 1, 2, 3, 8, 15, and 22 in the absence of disease progression or unacceptable toxicity.
- Maintenance phase: Patients receive sargramostim followed by glioblastoma multiform multi-antigen vaccine IMA950 ID on days 50 and 78 and then on day 21 of each adjuvant temozolomide course, beginning in course 1, for 3 courses in the absence of disease progression or unacceptable toxicity.
- Cohort 2: Vaccination begins at least 7 days after chemoradiotherapy and 28 days prior to adjuvant temozolomide.
- Induction phase: Patients receive the first 6 doses of sargramostim followed by glioblastoma multiform multi-antigen vaccine IMA950 ID as in cohort 1 induction phase, beginning at a different time point.
- Maintenance phase: Patients receive sargramostim followed by glioblastoma multiform multi-antigen vaccine IMA950 ID on day 21 of each adjuvant temozolomide course, beginning in course 1, for 5 courses in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for pharmacodynamic, biomarker, and immunologic studies.
After completion of study treatment, patients are followed at 41 weeks.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- glioblastoma multiforme multipeptide vaccine IMA950, sargramostim, temozolomide, laboratory biomarker analysis, pharmacological study
- Keywords
- adult gliosarcoma, adult giant cell glioblastoma, adult glioblastoma
- Medical subject headings
- Central Nervous System Neoplasms, Gliosarcoma, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
glioblastoma multiforme multipeptide vaccine IMA950Biological
sargramostimBiological
temozolomideDrug
laboratory biomarker analysisOther
adjuvant therapyProcedure or surgery
radiation therapyRadiation
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2010 (estimated)
- Study startJul 2010
- Primary completionFeb 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cancer Research UK
- Sponsor type
- University, hospital or other
- Collaborators
- Immatics Biotechnologies GmbH
- Responsible party
- Sponsor
- Investigators
- Roy Rampling, MD, PhD, Principal investigator, University of Glasgow
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01222221
- Sponsor's protocol ID
- CDR0000686559
- Other IDs
- CRUK-CR0902-11, EUDRACT-2009-015971-28
- Status last verified
- Oct 2015
- First submitted
- 14 Oct 2010
- Last updated
- 14 Oct 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01222221
- Acronym / sponsor ID
- CDR0000686559
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- adult gliosarcoma, adult giant cell glioblastoma, adult glioblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Cancer Research UKUniversity, hospital or other
- Collaborators
- Immatics Biotechnologies GmbH
- Study start
- Jul 2010
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 18 Oct 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
Primary
- To assess the safety and tolerability of glioblastoma multiform multi-antigen vaccine IMA950 plus sargramostim (GM-CSF) in combination with standard chemoradiotherapy comprising temozolomide and radiotherapy followed by adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme.
- To determine the immunogenicity of this regimen in these patients.
Secondary
- To determine the anti-tumor effect of this regimen in these patients.
- To determine the effect of pre-treatment levels of regulatory T-cells on the immunogenicity of this regimen in these patients. (Exploratory)
- To evaluate the potential effect of steroid dose on the immunological response to glioblastoma multiform multi-antigen vaccine IMA950 plus GM-CSF.
Tertiary
- To assess the level of O6-methyl-DNA-methyltransferase (MGMT) promoter methylation in tumor tissue and any potential association with any observed anti-tumor effect.
- To evaluate the kinetics of the observed immunogenicity of glioblastoma multiform multi-antigen vaccine IMA950 plus GM-CSF.
- To explore the possible biomarker signatures that may predict immunological response to glioblastoma multiform multi-antigen vaccine IMA950 plus GM-CSF. (Exploratory)
- To explore the possible effects of this regimen on any observed pseudo-progression and pseudo-regression in these patients. (exploratory)
OUTLINE: This is a multicenter study. Patients are recruited to cohort 1 or 2 with priority recruitment to cohort 1. All patients undergo standard chemoradiotherapy followed by adjuvant temozolomide as planned.
- Standard therapy (chemoradiotherapy and adjuvant temozolomide): Beginning after surgery, patients receive chemoradiotherapy comprising oral temozolomide daily for 6 weeks and radiotherapy once daily, 5 days a week for 6 weeks. Beginning 35 days after completion of radiotherapy, patients receive adjuvant oral temozolomide alone on days 1-5. Treatment with temozolomide repeats every 28 days for 6 courses.
- Vaccine therapy: Patients also receive vaccine therapy beginning at one of two time points. Patients are recruited into 1 of 2 cohorts that differ in the timing of the vaccination schedule in relation to a patient's standard therapy.
- Cohort 1: Vaccination begins 7-14 days prior to chemoradiotherapy.
- Induction phase: Patients receive the first 6 doses of sargramostim intradermally (ID) followed by glioblastoma multiform multi-antigen vaccine IMA950 ID on days 1, 2, 3, 8, 15, and 22 in the absence of disease progression or unacceptable toxicity.
- Maintenance phase: Patients receive sargramostim followed by glioblastoma multiform multi-antigen vaccine IMA950 ID on days 50 and 78 and then on day 21 of each adjuvant temozolomide course, beginning in course 1, for 3 courses in the absence of disease progression or unacceptable toxicity.
- Cohort 2: Vaccination begins at least 7 days after chemoradiotherapy and 28 days prior to adjuvant temozolomide.
- Induction phase: Patients receive the first 6 doses of sargramostim followed by glioblastoma multiform multi-antigen vaccine IMA950 ID as in cohort 1 induction phase, beginning at a different time point.
- Maintenance phase: Patients receive sargramostim followed by glioblastoma multiform multi-antigen vaccine IMA950 ID on day 21 of each adjuvant temozolomide course, beginning in course 1, for 5 courses in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for pharmacodynamic, biomarker, and immunologic studies.
After completion of study treatment, patients are followed at 41 weeks.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| glioblastoma multiforme multipeptide vaccine IMA950 | Biological | – |
| sargramostim | Biological | – |
| temozolomide | Drug | – |
| laboratory biomarker analysis | Other | – |
| pharmacological study | Other | – |
| adjuvant therapy | Procedure or surgery | – |
| radiation therapy | Radiation | – |
Primary outcome
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
4 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roy Rampling, MD, PhD principal investigator
University of Glasgow
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing glioblastoma multiforme multipeptide vaccine IMA950, sargramostim and temozolomide in people with Brain and Central Nervous System Tumors, run by Cancer Research UK at 7 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2015.