Glioblastoma MultiformePhase 1NCT02510950
Neoepitope-based Personalized Vaccine Approach in Patients With Newly Diagnosed Glioblastoma
A Phase 1 study testing Personalized peptide vaccine, Poly-ICLC and Temozolomide in people with Glioblastoma Multiforme and Astrocytoma, Grade IV, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The early clinical development paradigm for chemotherapeutic agents has significantly influenced the development of therapeutic cancer vaccines. However, there are major differences between these two classes of therapeutics that have important implications for early clinical development. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme, Astrocytoma, Grade IV
- What is being tested?
- Personalized peptide vaccine, Poly-ICLC and Temozolomide
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Dec 2015to 14 Feb 2017
- 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
Who may be able to join
- Newly diagnosed histologically confirmed glioblastoma multiforme (WHO grade IV). Patients with secondary glioblastoma, in particular those who are IDH1 or IDH2 mutant, will not be excluded.
- Patients who had craniotomy with biopsy, subtotal resection, total gross resection, or re-resection will be permitted.
- Consented to genome sequencing and dbGaP-based data sharing and has provided or will provide germline (PBMC) and tumor DNA/RNA samples of adequate quality for sequencing. (Acquisition of specimens for sequencing and the sequencing itself may be done under this study or as part of routine care or another research project.)
- At least 18 years of age.
- Karnofsky performance status ≥ 60%
- Normal bone marrow and organ function as defined below:
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- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- Systemic corticosteroid therapy is permitted provided dosing is no greater than 4 mg per day (dexamethasone or equivalent) on the day of vaccine administration
- Bevacizumab will be allowed if given for symptomatic control of vasogenic edema and to avoid high dose of corticosteroids
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Who cannot join
- As this is a safety and feasibility study, prior immunotherapy will be permitted. However, any prior immunotherapy must be discontinued at least 2 weeks before peptide vaccine administration. Non-immunologic therapy may be continued.
- Inadequate tissue acquisition to allow for neoantigen screening
- No candidate neoantigen identified during screening
- A history of other malignancy ≤ 3 years previous with the exception of non-melanoma skin cancer, any in situ cancer that has been successfully resected and cured, treated superficial bladder cancer, or any early-stage solid tumor that was successfully resected without need for adjuvant radiation or chemotherapy.
- Currently receiving any other investigational agents.
- Known allergy, or history of serious adverse reaction to, vaccines such as anaphylaxis, hives, or respiratory difficulty.
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- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to poly-ICLC or other agents used in the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- History of pre-existing immunodeficiency disorder including chronic infection (i.e. hepatitis B, hepatitis C, HIV), or autoimmune condition requiring immunosuppressive therapy. This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines.
- Presence of clinically significant increased intracranial pressure (e.g. impending herniation) or hemorrhage, uncontrolled seizures, or requirement for immediate palliative treatment.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of first dose of vaccine.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Pilot Study to Assess the Safety, Feasibility, and Preliminary Efficacy of a Neoepitope-based Personalized Vaccine Approach in Patients With Newly Diagnosed Glioblastoma
The early clinical development paradigm for chemotherapeutic agents has significantly influenced the development of therapeutic cancer vaccines. However, there are major differences between these two classes of therapeutics that have important implications for early clinical development. Specifically, the phase 1 concept of dose escalation to find a maximum-tolerated dose does not apply to most therapeutic cancer vaccines. Most therapeutic cancer vaccines are associated with minimal toxicity at a range that is feasible to manufacture or administer, and there is little reason to believe that the maximum-tolerated dose is the most effective dose.
In a recent article from the biostatistics literature, Simon et al. write that "the initial clinical trial of many new vaccines will not be a toxicity or dose-ranging trial but rather will involve administration of a fixed dose of vaccine … in most cases the dose selected will be based on preclinical findings or practical considerations. Using several dose levels in the initial study to find the minimal active dose or to characterize the dose-activity relationship is generally not realistic".
Consistent with these recommendations, the general philosophy of the phase 1 clinical trial is to facilitate a prompt preliminary evaluation of the safety and immunogenicity of the personalized synthetic long peptide vaccine strategy. The proposed clinical trial will test a fixed dose of vaccine. There is considerable experience with the synthetic long peptide vaccine platform. The synthetic long peptide vaccine platform has an excellent safety profile, and the optimal dose appears to be based on practical considerations (solubility of the peptide). The dose to be tested in the proposed clinical trial is consistent with other similar cancer vaccine trials that have been recently completed or are currently ongoing. The sample size (n=10) will provide a reasonably reliable estimate of the safety and immunogenicity of the vaccine.
- Conditions
- Glioblastoma Multiforme, Astrocytoma, Grade IV
- Being tested
- Personalized peptide vaccine, Poly-ICLC, Temozolomide
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Personalized peptide vaccineBiological
Poly-ICLCDrug
Also called Hiltonol
TemozolomideDrug
Also called Temodar®
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Peptide/poly-ICLC | Experimental | * For all patients, concurrent chemoradiation with temozolomide will be given per standard of care and is outside the scope of this study as per standard of care.
* The long peptide + poly-ICLC will be given on Cycle 1 Day 1 of maintenance temozolomide.
* If the vaccine is not ready by this time, the first vaccination will begin on Day 1 of the next cycle of maintenance temozolomide.
* The peptide + poly-ICLC vaccine will be given again on Days 8, 15, and 22 of the first cycle, as a priming strategy.
* On all subsequent cycles, the peptide vaccine + poly-ICLC will be given on Day 22 (+/-3 days). Receives: Biological: Personalized peptide vaccine; Drug: Poly-ICLC; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of adjuvant personalized neoantigen peptide vaccine with poly-ICLC as measured by grade 3 and 4 adverse events as defined by CTCAE v. 4.03
Measured: 30 days after completion of treatment (approximately 7 months)
Feasibility of the peptide vaccine with poly-ICLC as measured by the ability to identify patient tumor-derived candidate neoantigens and generate a tumor-specific vaccine from time of initial diagnosis to time of proposed administration of the vaccine
Measured: Approximately 12-14 weeks
Secondary outcomes (3)
Progression-free survival (PFS) rate
- PFS: duration of time from start of treatment to time of progression or death, whichever occurs first.
- Progression will be evaluated using the updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology (RANO) working group guideline
Measured: Up to 24 months after last dose of vaccine
Overall survival (OS) rate
OS: duration of time from start of treatment to time of death from any cause
Measured: Up to 24 months after last dose of vaccine
Number of neoantigens present in patients with newly diagnosed GBM
Measured: After completion of treatment (approximately 6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2015 (estimated)
- Study start3 Dec 2015
- Primary completion14 Feb 2017
- Study completion14 Feb 2017
Why it stopped: Low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gavin Dunn, M.D., Ph.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02510950
- Sponsor's protocol ID
- 201510022
- Status last verified
- Nov 2017
- First submitted
- 27 Jul 2015
- Last updated
- 17 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Assess the Safety, Feasibility, and Preliminary Efficacy of a Neoepitope-based Personalized Vaccine Approach in Patients With Newly Diagnosed Glioblastoma
- ClinicalTrials.gov ID
- NCT02510950
- Acronym / sponsor ID
- 201510022
- Conditions
- Glioblastoma Multiforme, Astrocytoma, Grade IV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 3 Dec 2015 (actual)
- Primary completion
- 14 Feb 2017 (actual)
- Study completion
- 14 Feb 2017 (actual)
- First posted
- 29 Jul 2015 (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.
The early clinical development paradigm for chemotherapeutic agents has significantly influenced the development of therapeutic cancer vaccines. However, there are major differences between these two classes of therapeutics that have important implications for early clinical development. Specifically, the phase 1 concept of dose escalation to find a maximum-tolerated dose does not apply to most therapeutic cancer vaccines. Most therapeutic cancer vaccines are associated with minimal toxicity at a range that is feasible to manufacture or administer, and there is little reason to believe that the maximum-tolerated dose is the most effective dose.
In a recent article from the biostatistics literature, Simon et al. write that "the initial clinical trial of many new vaccines will not be a toxicity or dose-ranging trial but rather will involve administration of a fixed dose of vaccine … in most cases the dose selected will be based on preclinical findings or practical considerations. Using several dose levels in the initial study to find the minimal active dose or to characterize the dose-activity relationship is generally not realistic".
Consistent with these recommendations, the general philosophy of the phase 1 clinical trial is to facilitate a prompt preliminary evaluation of the safety and immunogenicity of the personalized synthetic long peptide vaccine strategy. The proposed clinical trial will test a fixed dose of vaccine. There is considerable experience with the synthetic long peptide vaccine platform. The synthetic long peptide vaccine platform has an excellent safety profile, and the optimal dose appears to be based on practical considerations (solubility of the peptide). The dose to be tested in the proposed clinical trial is consistent with other similar cancer vaccine trials that have been recently completed or are currently ongoing. The sample size (n=10) will provide a reasonably reliable estimate of the safety and immunogenicity of the vaccine.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Peptide/poly-ICLC | Experimental | Biological: Personalized peptide vaccine, Drug: Poly-ICLC, Drug: Temozolomide* For all patients, concurrent chemoradiation with temozolomide will be given per standard of care and is outside the scope of this study as per standard of care. * The long peptide + poly-ICLC will be given on Cycle 1 Day 1 of maintenance temozolomide. * If the vaccine is not ready by this time, the first vaccination will begin on Day 1 of the next cycle of maintenance temozolomide. * The peptide + poly-ICLC vaccine will be given again on Days 8, 15, and 22 of the first cycle, as a priming strategy. * On all subsequent cycles, the peptide vaccine + poly-ICLC will be given on Day 22 (+/-3 days). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Newly diagnosed histologically confirmed glioblastoma multiforme (WHO grade IV). Patients with secondary glioblastoma, in particular those who are IDH1 or IDH2 mutant, will not be excluded.
- Patients who had craniotomy with biopsy, subtotal resection, total gross resection, or re-resection will be permitted.
- Consented to genome sequencing and dbGaP-based data sharing and has provided or will provide germline (PBMC) and tumor DNA/RNA samples of adequate quality for sequencing. (Acquisition of specimens for sequencing and the sequencing itself may be done under this study or as part of routine care or another research project.)
- At least 18 years of age.
- Karnofsky performance status ≥ 60%
Key exclusion criteria (11 listed)
- As this is a safety and feasibility study, prior immunotherapy will be permitted. However, any prior immunotherapy must be discontinued at least 2 weeks before peptide vaccine administration. Non-immunologic therapy may be continued.
- Inadequate tissue acquisition to allow for neoantigen screening
- No candidate neoantigen identified during screening
- A history of other malignancy ≤ 3 years previous with the exception of non-melanoma skin cancer, any in situ cancer that has been successfully resected and cured, treated superficial bladder cancer, or any early-stage solid tumor that was successfully resected without need for adjuvant radiation or chemotherapy.
- Currently receiving any other investigational agents.
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 |
|---|---|---|
| Personalized peptide vaccine | Biological | Arm 1: Peptide/poly-ICLC |
| Poly-ICLCAlso: Hiltonol | Drug | Arm 1: Peptide/poly-ICLC |
| TemozolomideAlso: Temodar® | Drug | Arm 1: Peptide/poly-ICLC |
Primary outcome
Safety and tolerability of adjuvant personalized neoantigen peptide vaccine with poly-ICLC as measured by grade 3 and 4 adverse events as defined by CTCAE v. 4.03
Time frame: 30 days after completion of treatment (approximately 7 months)
Feasibility of the peptide vaccine with poly-ICLC as measured by the ability to identify patient tumor-derived candidate neoantigens and generate a tumor-specific vaccine from time of initial diagnosis to time of proposed administration of the vaccine
Time frame: Approximately 12-14 weeks
3 secondary outcomes
Progression-free survival (PFS) rate
Time frame: Up to 24 months after last dose of vaccine
Overall survival (OS) rate
Time frame: Up to 24 months after last dose of vaccine
Number of neoantigens present in patients with newly diagnosed GBM
Time frame: After completion of treatment (approximately 6 months)
Results and safety
The study was stopped early (reason given: Low accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2017.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Gavin Dunn, M.D., Ph.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Personalized peptide vaccine, Poly-ICLC and Temozolomide in people with Glioblastoma Multiforme and Astrocytoma, Grade IV, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 11 exclusion criteria. 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: stopped early, as of the sponsor's last update on 17 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 was stopped early (reason given: Low accrual). Results are not available in the source record.
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?
Safety and tolerability of adjuvant personalized neoantigen peptide vaccine with poly-ICLC as measured by grade 3 and 4 adverse events as defined by CTCAE v. 4.03 (time frame: 30 days after completion of treatment (approximately 7 months)). 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 17 Nov 2017.