GlioblastomaPhase 2NCT02754362
A Toll-like Receptor Agonist as an Adjuvant to Tumor Associated Antigens (TAA) Mixed With Montanide ISA-51 VG With Bevacizumab for Patients With Recurrent Glioblastoma
A Phase 2 study testing Bevacizumab, Peptide Vaccine and Poly-ICLC as immune adjuvant in people with Glioblastoma and Glioma, run by NYU Langone Health at 1 site in United States.
Trial summary
This is a phase II study to determine the immunogenicity and efficacy of a vaccine composed of tumor associated long synthetic peptides mixed with Montanide ISA-51 VG administered with polyinosinic-polycytidylic acid - poly-L-lysine carboxymethylcellulose (Poly-ICLC) and bevacizumab in adults with recurrent… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Glioma
- What is being tested?
- Bevacizumab, Peptide Vaccine and Poly-ICLC as immune adjuvant
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2016to Jun 2019
- Phase
- Phase 2
- 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
- Disease Status. Patients with first recurrence of glioblastoma (WHO IV). Patients must have histological confirmation of glioblastoma (WHO grade IV) either at diagnosis or at first recurrence. Patients with diffuse intrinsic pontine glioma (DIPG) are not eligible.
- Karnofsky performance status > 50. Patients who are unable to walk because of paralysis but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- Adequate organ function:
- Hematologic: absolute lymphocyte count > 200/mm3 Platelets > 100,000 Hepatic:AST/ALT < 5 x the upper limit of institutional normal Total bilirubin < 1.5 x the upper limit of institutional normal Renal: serum creatinine < 1.5 mg/ml; Urine protein/creatinine ratio < 2.0 at screening Cardiac: Hypertension must be well controlled on stable doses of medication. BP must be < 140/90.
- Life expectancy >3 months
- Patients must have fully recovered from previous surgery, chemotherapy, radiotherapy and biologic therapy. No surgery, chemotherapy, radiation therapy or immunotherapy within 4 weeks prior to the first dose of study agent or bevacizumab (6 weeks for nitrosureas).
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- Patients must have no measurable disease or minimal residual disease defined as <1.5cm2 enhancement. Patients may have surgery to achieve < 1.5cm2 residual.
- Tumor tissue must be available either from initial diagnosis or relapse for testing of antigen expression.
- Informed consent must be signed by the patient. Individuals who lack capacity to sign consent will be excluded. Patients must be able to read and/or understand the details of the study and provide written evidence of informed consent as approved by the IRB.
Who cannot join
- Serious illness, such as uncontrolled infections requiring antibiotics
- History of immunodeficiency disease (such as HIV) or autoimmune disease except vitiligo
- Concomitant treatment with systemic dexamethasone (or it's equivalent) greater than 2mg/day. Topical (but not at the proposed vaccination site) or inhalational steroids are permitted
- Participation in any other clinical trial involving another investigational agent within 4 weeks prior the first dose of study agent.
- Pregnant or lactating women are not permitted.
- Women of child-bearing potential not using medically acceptable means of contraception.
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- Prior vaccine therapy for high grade glioma is not allowed.
- Other malignancy within 3 years prior to entry into the study, except for treated early-stage melanoma or non-melanoma skin cancer, or cervical carcinoma in situ
- Significant bleeding history
- Patients with serious or non-healing wound, ulcer, or bone fractures are not eligible.
- Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry.
- Patients must not have a known bleeding diathesis or coagulopathy.
- Patients must not have had significant vascular disease (eg, aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to study entry.
- Patients must not have evidence of new CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment.
- Patients must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome). Testing is not required in patients without thrombophilic history.
- Patients must not have a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure within the past 6 months prior to study entry.
- Patients must not have serious and inadequately controlled cardiac arrhythmias.
- Patients must not have a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the first dose of bevacizumab or anticipation of need for major surgical procedure during the course of the study.
- Patients must not have minor surgical procedures, fine needle aspirations, or core biopsies within 7 days prior to study enrollment.
- Patients with organ allografts.
Trial locations and contacts
1 site in 1 country.
United States1 site
NYU Perlmutter Cancer Center
New York, New York, 10016
About this study
This is a phase II study to determine the immunogenicity and efficacy of a vaccine composed of tumor associated long synthetic peptides mixed with Montanide ISA-51 VG administered with polyinosinic-polycytidylic acid - poly-L-lysine carboxymethylcellulose (Poly-ICLC) and bevacizumab in adults with recurrent glioblastoma.
Read the detailed description
All patients will receive the same dose of vaccine, Poly-ICLC and bevacizumab. The therapy consists of 3 blocks. During the first block, patients will receive bevacizumab every 2 weeks for 2 doses. During block 2, patients will receive vaccine + Poly-ICLC + bevacizumab on weeks 1, 3, 5 and 7. An MRI will be performed after week 7 therapy. If there is no significant progression, then the patients will continue with block 3. During block 3, therapy consists of vaccine + Poly-ICLC monthly and bevacizumab every 2 weeks for 10 months. Keyhole limpet hemocyanin (KLH) will be given as a positive control with the first vaccine. Immune studies will be performed in all patients enrolled in this study.
- Conditions
- Glioblastoma, Glioma
- Being tested
- Bevacizumab, Peptide Vaccine, Poly-ICLC as immune adjuvant, Keyhole limpet hemocyanin (KLH)
- Keywords
- Poly-ICLC and bevacizumab, humanized monoclonal antibody
- Medical subject headings
- Glioblastoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Hiltonol®
Bevacizumab is a humanized monoclonal antibody that targets vascular endothelial growth factor (VEGF), a proangiogenic factor which aids in tumor vessel formation.
Peptide VaccineBiological
Vaccine of long synthetic peptides encoding T cell epitopes in tumor associated antigens.
Vaccine Consists of:
EGFRvIII peptide 100 mcg IL13Ralpha peptide 100 mcg EphA2 peptide 100 mcg Her2/neu peptide 100 mcg YKL-40 peptide 100 mcg
Poly-ICLC as immune adjuvantDrug
Poly-ICLC is a toll like receptor 3 agonist which directly activates dendritic cells and triggers natural killer cells to kill tumor cells.
Keyhole limpet hemocyanin (KLH)Drug
Potent Immunogen used in vaccine approaches for a number of diseases including cancer, AIDS, and infectious diseases
| Study group | Role | What they receive |
|---|---|---|
| Block 1 | Experimental | Not described Receives: Drug: Bevacizumab |
| Block 2 | Experimental | Not described Receives: Drug: Bevacizumab; Biological: Peptide Vaccine; Drug: Poly-ICLC as immune adjuvant; Drug: Keyhole limpet hemocyanin (KLH) |
| Block 3 | Experimental | Not described Receives: Drug: Bevacizumab; Biological: Peptide Vaccine; Drug: Poly-ICLC as immune adjuvant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assays to determine immunity to the vaccine's antigen
Measured: 9 Weeks
Measure of Humoral Immune Responses measured by ELISA
Measured: 9 Weeks
Antigen specific CD4+ and CD8+ T-cell reactivity to the peptide antigens measured by intracellular cytokine staining
Measured either ex-vivo (assayed directly from thawed PBMCs) or following in-vitro pre-sensitization.
Measured: 9 Weeks
CD4+ and CD8+ T cell reactivity to KLH measured by T cell proliferation quantified by tritiated thymidine incorporation
Measured: 9 Weeks
Measure of Tumor Responses measured by the Response Evaluation Criteria in Solid Tumors (RECIST).
Measured: 1 Day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2016 (estimated)
- Study startNov 2016
- Primary completionJun 2019 (estimated)
- Study completionJun 2019 (estimated)
Why it stopped: Due to personnel changes / departure of Dr. Chi.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- MOUNT SINAI HOSPITAL
- Responsible party
- Sponsor
- Investigators
- Sharon Gardner, MD, Principal investigator, New York University Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02754362
- Sponsor's protocol ID
- 15-00044
- Status last verified
- Jan 2020
- First submitted
- 13 Apr 2016
- Last updated
- 13 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Toll-like Receptor Agonist as an Adjuvant to Tumor Associated Antigens (TAA) Mixed With Montanide ISA-51 VG With Bevacizumab for Patients With Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT02754362
- Acronym / sponsor ID
- 15-00044
- Conditions
- Glioblastoma, Glioma
- Keywords
- Poly-ICLC and bevacizumab, humanized monoclonal antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Due to personnel changes / departure of Dr. Chi.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- MOUNT SINAI HOSPITAL
- Study start
- Nov 2016 (actual)
- Primary completion
- Jun 2019 (estimated)
- Study completion
- Jun 2019 (estimated)
- First posted
- 28 Apr 2016 (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.
This is a phase II study to determine the immunogenicity and efficacy of a vaccine composed of tumor associated long synthetic peptides mixed with Montanide ISA-51 VG administered with polyinosinic-polycytidylic acid - poly-L-lysine carboxymethylcellulose (Poly-ICLC) and bevacizumab in adults with recurrent glioblastoma.
Detailed description
All patients will receive the same dose of vaccine, Poly-ICLC and bevacizumab. The therapy consists of 3 blocks. During the first block, patients will receive bevacizumab every 2 weeks for 2 doses. During block 2, patients will receive vaccine + Poly-ICLC + bevacizumab on weeks 1, 3, 5 and 7. An MRI will be performed after week 7 therapy. If there is no significant progression, then the patients will continue with block 3. During block 3, therapy consists of vaccine + Poly-ICLC monthly and bevacizumab every 2 weeks for 10 months. Keyhole limpet hemocyanin (KLH) will be given as a positive control with the first vaccine. Immune studies will be performed in all patients enrolled in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Block 1 | Experimental | Drug: Bevacizumab |
| Block 2 | Experimental | Drug: Bevacizumab, Biological: Peptide Vaccine, Drug: Poly-ICLC as immune adjuvant, Drug: Keyhole limpet hemocyanin (KLH) |
| Block 3 | Experimental | Drug: Bevacizumab, Biological: Peptide Vaccine, Drug: Poly-ICLC as immune adjuvant |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Disease Status. Patients with first recurrence of glioblastoma (WHO IV). Patients must have histological confirmation of glioblastoma (WHO grade IV) either at diagnosis or at first recurrence. Patients with diffuse intrinsic pontine glioma (DIPG) are not eligible.
- Karnofsky performance status > 50. Patients who are unable to walk because of paralysis but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- Adequate organ function:
- Hematologic: absolute lymphocyte count > 200/mm3 Platelets > 100,000 Hepatic:AST/ALT < 5 x the upper limit of institutional normal Total bilirubin < 1.5 x the upper limit of institutional normal Renal: serum creatinine < 1.5 mg/ml; Urine protein/creatinine ratio < 2.0 at screening Cardiac: Hypertension must be well controlled on stable doses of medication. BP must be < 140/90.
- Life expectancy >3 months
Key exclusion criteria (20 listed)
- Serious illness, such as uncontrolled infections requiring antibiotics
- History of immunodeficiency disease (such as HIV) or autoimmune disease except vitiligo
- Concomitant treatment with systemic dexamethasone (or it's equivalent) greater than 2mg/day. Topical (but not at the proposed vaccination site) or inhalational steroids are permitted
- Participation in any other clinical trial involving another investigational agent within 4 weeks prior the first dose of study agent.
- Pregnant or lactating women are not permitted.
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 |
|---|---|---|
| BevacizumabAlso: Hiltonol®Bevacizumab is a humanized monoclonal antibody that targets vascular endothelial growth factor (VEGF), a proangiogenic factor which aids in tumor vessel formation. | Drug | Block 1, Block 2, Block 3 |
| Peptide VaccineVaccine of long synthetic peptides encoding T cell epitopes in tumor associated antigens. Vaccine Consists of: EGFRvIII peptide 100 mcg IL13Ralpha peptide 100 mcg EphA2 peptide 100 mcg Her2/neu peptide 100 mcg YKL-40 peptide 100 mcg | Biological | Block 2, Block 3 |
| Poly-ICLC as immune adjuvantPoly-ICLC is a toll like receptor 3 agonist which directly activates dendritic cells and triggers natural killer cells to kill tumor cells. | Drug | Block 2, Block 3 |
| Keyhole limpet hemocyanin (KLH)Potent Immunogen used in vaccine approaches for a number of diseases including cancer, AIDS, and infectious diseases | Drug | Block 2 |
Primary outcome
Assays to determine immunity to the vaccine's antigen
Time frame: 9 Weeks
Measure of Humoral Immune Responses measured by ELISA
Time frame: 9 Weeks
Antigen specific CD4+ and CD8+ T-cell reactivity to the peptide antigens measured by intracellular cytokine staining
Time frame: 9 Weeks
Measured either ex-vivo (assayed directly from thawed PBMCs) or following in-vitro pre-sensitization.
CD4+ and CD8+ T cell reactivity to KLH measured by T cell proliferation quantified by tritiated thymidine incorporation
Time frame: 9 Weeks
Measure of Tumor Responses measured by the Response Evaluation Criteria in Solid Tumors (RECIST).
Time frame: 1 Day
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 13 Jan 2020.
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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.
Sharon Gardner, MD principal investigator
New York University Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab, Peptide Vaccine and Poly-ICLC as immune adjuvant in people with Glioblastoma and Glioma, run by NYU Langone Health 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 9 inclusion and 20 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 13 Jan 2020. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Assays to determine immunity to the vaccine's antigen (time frame: 9 Weeks). The study lists 5 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 13 Jan 2020.