Pediatric Brain TumorPhase 1NCT03068832
Neoepitope-based Personalized Vaccine Approach in Pediatric Patients With Recurrent Brain Tumors
A Phase 1 study testing Personalized peptide vaccine, Poly ICLC and Peripheral blood draw in people with Pediatric Brain Tumor, run by Washington University School of Medicine.
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 Up to 21 years
- Conditions the study is for
- Pediatric Brain Tumor
- What is being tested?
- Personalized peptide vaccine, Poly ICLC and Peripheral blood draw
- Type of treatment
- Vaccines, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 30 Sep 2021to 28 Feb 2026
- 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Any patient, regardless of current age, who was diagnosed between the ages of 0-21 years with a pediatric brain tumor of any histologic subtype, who has now developed recurrent or refractory disease.
- Availability of tissue for sequencing to determine presence of targetable neoantigen. This may be fresh tissue collected as part of routine care, another research project or archived tissue from a previous craniotomy with biopsy, subtotal resection, total gross resection, or re-resection.
- Karnofsky/Lansky performance status ≥ 60%
- Normal bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
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- Total bilirubin ≤ 1.5 x institutional upper limit of normal (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 minimal based on age 0.1mg/kg/day with a max of 4mg daily (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 at the discretion of the treating physician.
- 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.
- 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.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to poly-ICLC or other agents used in the study.
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- 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, autoimmune condition requiring immunosuppressive therapy, or chronic infection (i.e. hepatitis B, hepatitis C, HIV). 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, Sjögren'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.
About this study
Official title: A Pilot Study to Assess the Safety, Feasibility, and Preliminary Efficacy of a Neoepitope-based Personalized Vaccine Approach in Pediatric Patients With Recurrent Brain Tumors
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=10-20) will provide a reasonably reliable estimate of the safety and immunogenicity of the vaccine.
- Conditions
- Pediatric Brain Tumor
- Being tested
- Personalized peptide vaccine, Poly ICLC, Peripheral blood draw
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Personalized peptide vaccineBiological
-It may take 3-4 months for sequencing, neoantigen prediction, and peptide manufacturing
Poly ICLCDrug
Also called Poly-ICLC, Hiltonol
-Poly-ICLC is supplied by Oncovir in single-dose vials containing 1 mL of 2 mg/mL opalescent white suspension.
Peripheral blood drawProcedure or surgery
- After trial enrollment and up to 7 days after the 1st vaccine dose
- 2 weeks after last dose
- Time of progression or discontinuation
| Study group | Role | What they receive |
|---|---|---|
| Personalized peptide vaccine and poly-ICLC | Experimental | * The synthetic long peptide(s) and poly-ICLC will be given on Cycle 1 Day 1 when available.
* Additional peptide vaccine doses will be administered again on Days 4, 8, 15, and 22 of the first cycle as a priming strategy. On all subsequent cycles, the peptide vaccine will be given on Day 1.
* Peptide vaccine administration will continue until supply is exhausted or development of intolerance or disease progression in the case of fatal high grade neoplasms. Otherwise, vaccination will continue until supply is exhausted or intolerance or one year for non-fatal tumors. Additionally, patients with non-fatal tumors who complete one year of vaccinations and have stable disease will be given the option of resuming vaccinations if they develop subsequent progression if remaining vaccine is available. Receives: Biological: Personalized peptide vaccine; Drug: Poly ICLC; Procedure: Peripheral blood draw |
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 administration with poly-ICLC as measured by grade 3 and 4 adverse events
-As defined by CTCAE v. 4.03
Measured: Up to 30 days following last day of study treatment (up to 4 months)
Feasibility of adjuvant personalized neoantigen peptide vaccine administration with poly-ICLC as measured by the number of participants who have a neoantigen specific long peptide vaccine identified and generated
-The vaccine study drug is a frozen solution for injection. It is a personalized vaccine composed of up to 20 synthesized peptides that are approximately 20 to 35 amino acids in length. The peptides are designed to generate an immune response to neoantigens found in each patient's tumor.
Measured: 12-14 weeks
Secondary outcomes (2)
Characterize tumor-infiltrating lymphocytes (TIL)
-Paired t-test or paired-sample Wilcoxon Signed Rank test will be used to compare the gene expression of TIL in blood as measured before and after treatment.
Measured: Up to 2 weeks after the last dose (up to 4 months)
Frequency of expressed neoantigens using patient-specific HLA class I prediction algorithms
-Up to 20 of the highest priority sequencing-identified mutant tumor-specific antigens that are confirmed to bind and stabilize HLA class I molecules will be targeted
Measured: Completion of treatment (up to 3 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2017
- Study start30 Sep 2021 (estimated)
- Primary completion31 Mar 2023 (estimated)
- Study completion28 Feb 2026 (estimated)
Why it stopped: Made the decision to not go forward with the study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pediatric Brain TumorStudies 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joshua Rubin, M.D., Ph.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03068832
- Sponsor's protocol ID
- 201807123
- Status last verified
- May 2021
- First submitted
- 27 Feb 2017
- Last updated
- 25 May 2021
- 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 25 May 2021. 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 Pediatric Patients With Recurrent Brain Tumors
- ClinicalTrials.gov ID
- NCT03068832
- Acronym / sponsor ID
- 201807123
- Conditions
- Pediatric Brain Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Made the decision to not go forward with the study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 30 Sep 2021 (estimated)
- Primary completion
- 31 Mar 2023 (estimated)
- Study completion
- 28 Feb 2026 (estimated)
- First posted
- 3 Mar 2017 (actual)
- 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=10-20) 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 |
|---|---|---|
| Personalized peptide vaccine and poly-ICLC | Experimental | Biological: Personalized peptide vaccine, Drug: Poly ICLC, Procedure: Peripheral blood draw* The synthetic long peptide(s) and poly-ICLC will be given on Cycle 1 Day 1 when available. * Additional peptide vaccine doses will be administered again on Days 4, 8, 15, and 22 of the first cycle as a priming strategy. On all subsequent cycles, the peptide vaccine will be given on Day 1. * Peptide vaccine administration will continue until supply is exhausted or development of intolerance or disease progression in the case of fatal high grade neoplasms. Otherwise, vaccination will continue until supply is exhausted or intolerance or one year for non-fatal tumors. Additionally, patients with non-fatal tumors who complete one year of vaccinations and have stable disease will be given the option of resuming vaccinations if they develop subsequent progression if remaining vaccine is available. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- Any patient, regardless of current age, who was diagnosed between the ages of 0-21 years with a pediatric brain tumor of any histologic subtype, who has now developed recurrent or refractory disease.
- Availability of tissue for sequencing to determine presence of targetable neoantigen. This may be fresh tissue collected as part of routine care, another research project or archived tissue from a previous craniotomy with biopsy, subtotal resection, total gross resection, or re-resection.
- Karnofsky/Lansky performance status ≥ 60%
- Normal bone marrow and organ function as defined below:
- Systemic corticosteroid therapy is permitted provided dosing is minimal based on age 0.1mg/kg/day with a max of 4mg daily (dexamethasone or equivalent) on the day of vaccine administration.
Key exclusion criteria (10 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.
- 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.
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-It may take 3-4 months for sequencing, neoantigen prediction, and peptide manufacturing | Biological | Personalized peptide vaccine and poly-ICLC |
| Poly ICLCAlso: Poly-ICLC, Hiltonol-Poly-ICLC is supplied by Oncovir in single-dose vials containing 1 mL of 2 mg/mL opalescent white suspension. | Drug | Personalized peptide vaccine and poly-ICLC |
| Peripheral blood draw* After trial enrollment and up to 7 days after the 1st vaccine dose * 2 weeks after last dose * Time of progression or discontinuation | Procedure or surgery | Personalized peptide vaccine and poly-ICLC |
Primary outcome
Safety and tolerability of adjuvant personalized neoantigen peptide vaccine administration with poly-ICLC as measured by grade 3 and 4 adverse events
Time frame: Up to 30 days following last day of study treatment (up to 4 months)
-As defined by CTCAE v. 4.03
Feasibility of adjuvant personalized neoantigen peptide vaccine administration with poly-ICLC as measured by the number of participants who have a neoantigen specific long peptide vaccine identified and generated
Time frame: 12-14 weeks
-The vaccine study drug is a frozen solution for injection. It is a personalized vaccine composed of up to 20 synthesized peptides that are approximately 20 to 35 amino acids in length. The peptides are designed to generate an immune response to neoantigens found in each patient's tumor.
2 secondary outcomes
Characterize tumor-infiltrating lymphocytes (TIL)
Time frame: Up to 2 weeks after the last dose (up to 4 months)
Frequency of expressed neoantigens using patient-specific HLA class I prediction algorithms
Time frame: Completion of treatment (up to 3 months)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2021.
- 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.
Joshua Rubin, M.D., Ph.D. principal investigator
Washington University School of Medicine
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Personalized peptide vaccine, Poly ICLC and Peripheral blood draw in people with Pediatric Brain Tumor, run by Washington University School of Medicine.
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 13 inclusion and 10 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: withdrawn, as of the sponsor's last update on 25 May 2021. Status can change between updates, so confirm with the study contact before making plans.
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 withdrawn before enrolling participants, so there are no results.
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 administration with poly-ICLC as measured by grade 3 and 4 adverse events (time frame: Up to 30 days following last day of study treatment (up to 4 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 25 May 2021.