SurVaxM Plus Adjuvant Temozolomide for Newly Diagnosed Glioblastoma (SURVIVE)
NCT ID: NCT05163080
Last Updated: 2024-02-26
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
ACTIVE_NOT_RECRUITING
PHASE2
247 participants
INTERVENTIONAL
2021-11-18
2024-08-18
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
SurVaxM Vaccine Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma
NCT02455557
Temozolomide and Survivin Long Peptide Vaccine (SurVaxM) for the Treatment of Patients With Progressing Metastatic Neuroendocrine Carcinomas
NCT06202066
Temozolomide Plus Bevacizumab in Supratentorial Glioblastoma in 70 Years and Older Patients With an Impaired Functional Status
NCT02898012
Bi-weekly Temozolomide Plus Bevacizumab for Adult Patients With Recurrent Glioblastoma Multiforme
NCT00883298
Amgen 386 for Recurrent Glioblastoma
NCT01290263
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Patients that are randomized to receive placebo will be treated with standard-of-care temozolomide plus an injection under the skin of saline (salt water) in Montanide (a milky white substance). Patients in this group will also receive a second separate injection of saline to simulate the injection of sargramostim that patient's in the SurVaxM group receive. These injections will be repeated at regular intervals according to a schedule.
The treatments in the two groups (SurVaxM and placebo groups) will be completely indistinguishable to patients and their treating doctors.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm A
Peptide Vaccine (SurVaxM) in emulsion with Montanide given together with locally administered Sargramostim plus adjuvant oral Temozolomide
SurVaxM
Consists of a synthetic peptide conjugate that stimulates immune responses capable of killing cancer cells that express the survivin molecule. Multiple copies of the multiplied peptide (SVN53-67/M57) are conjugated to Keyhole Limpet Hemocyanin (KLH) yielding a molecule designated as SVN53-67/M57-KLH. The SVN53-67/M57-KLH conjugate (SurVaxM)produces immune responses in mice and humans that are cross-reactive to the wild-type survivin molecule expressed by tumor cells. The survivin peptide in SurVaxM is a defined antigenic peptide comprised of 15 amino acids that encompass multiple epitopes capable of binding human MHC Class I and murine H2-Kb molecules. SurVaxM also contains a core antigenic epitope that has been modified by substitution of methionine for cysteine at amino acid position 57 (i.e., M57).
Arm B
Saline-Montanide emulsion with locally administered saline (instead of sargramostim) plus adjuvant oral temozolomide
SurVaxM
Consists of a synthetic peptide conjugate that stimulates immune responses capable of killing cancer cells that express the survivin molecule. Multiple copies of the multiplied peptide (SVN53-67/M57) are conjugated to Keyhole Limpet Hemocyanin (KLH) yielding a molecule designated as SVN53-67/M57-KLH. The SVN53-67/M57-KLH conjugate (SurVaxM)produces immune responses in mice and humans that are cross-reactive to the wild-type survivin molecule expressed by tumor cells. The survivin peptide in SurVaxM is a defined antigenic peptide comprised of 15 amino acids that encompass multiple epitopes capable of binding human MHC Class I and murine H2-Kb molecules. SurVaxM also contains a core antigenic epitope that has been modified by substitution of methionine for cysteine at amino acid position 57 (i.e., M57).
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
SurVaxM
Consists of a synthetic peptide conjugate that stimulates immune responses capable of killing cancer cells that express the survivin molecule. Multiple copies of the multiplied peptide (SVN53-67/M57) are conjugated to Keyhole Limpet Hemocyanin (KLH) yielding a molecule designated as SVN53-67/M57-KLH. The SVN53-67/M57-KLH conjugate (SurVaxM)produces immune responses in mice and humans that are cross-reactive to the wild-type survivin molecule expressed by tumor cells. The survivin peptide in SurVaxM is a defined antigenic peptide comprised of 15 amino acids that encompass multiple epitopes capable of binding human MHC Class I and murine H2-Kb molecules. SurVaxM also contains a core antigenic epitope that has been modified by substitution of methionine for cysteine at amino acid position 57 (i.e., M57).
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
1. Age ≥ 18 years of age.
2. Have a Karnofsky performance status ≥ 70 (i.e., the patient must be able to care for him/herself with occasional help from others; refer to Appendix A).
3 .Pathologically confirmed diagnosis of glioblastoma of the cerebrum.
4 .The result of tumor MGMT methylation study must be available.
5 .The result of tumor IDH-1 mutation test must be available.
6\. Have the following clinical laboratory values obtained within 14 days prior to registration:
1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
2. Platelets ≥ 100 x 109/L
3. Hemoglobin (Hgb) ≥ 9.0 g/dL
4. Total bilirubin: ≤ 1.5 x ULN
5. ALT and AST ≤ 4.0 x ULN
6. Creatinine ≤ 1.8 mg/dL
7. Prothrombin time (PT) within 1.5x normal limits
8. Activated partial thromboplastin time (aPPT) within 1.5x control
9. International Normalized Ration (INR) less than or equal to 1.5x control
7\. Patient must have no active bleeding or pathological condition that carries a high risk of bleeding (e.g., coagulopathy)
8\. Available results from a contrast-enhanced, post-operative brain MRI that was completed within 72 hours after surgery documenting either:
a. gross total resection consisting of no gadolinium enhancement; or b. near-total resection consisting of either ≤ 1 cm3 nodular (i.e. volumetric) enhancement or ≤ 100 mm2 in cross sectional area (i.e. linear enhancement). Note: Patients who undergo either stereotactic biopsy or open biopsy for tissue diagnosis, or partial tumor resection, and who subsequently have a definitive surgical resection may still be eligible for inclusion, provided that randomization can occur within 16 weeks of the date of surgical resection. To be eligible, such patients must still meet postoperative imaging entry criteria as defined in item #8 above.
9\. Patients must have completed initial radiation therapy with TMZ (chemoradiation) according to established Stupp protocol (Stupp, 2005) for the treatment of their glioblastoma (i.e., completed 6-week course of RT and completed ≥ 75% of a course of concurrent TMZ chemotherapy).
10\. Patients must be randomized within 16 weeks of surgical resection of their newly diagnosed glioblastoma.
11\. No evidence of progressive disease at the post-chemoradiation timepoint based on changes in: neurologic exam, corticosteroid use or radiographic progression (i.e., baseline MRI evaluation). (See Section 14.5 for suspected pseudo-progression.)
12\. Participants of child-bearing potential (not surgically sterile or postmenopausal) must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and have a negative pregnancy test prior to starting study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
13\. Dexamethasone dose less than or equal to 4 mg daily at time of study enrollment. Every reasonable effort should be made to reduce the dose of corticosteroids to the absolute minimum dose required to control neurologic symptoms prior to receiving SurVaxM.
14\. Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.
Exclusion Criteria
1. Recurrent or progressive glioblastoma.
2. Gliosarcoma, anaplastic astrocytoma, oligodendroglioma, ependymoma, low grade glioma or any histology other than glioblastoma.
3. Multicentric glioblastoma or glioblastoma involving the brainstem or cerebellum, or leptomeningeal or spinal extension present at diagnosis.
4. Residual contrast enhancement \> 1 cm3 on post-operative scan obtained within 72 hours of surgery.
5. Absence of MRI obtained within 72 hours of craniotomy documenting
≤ 1 cm3 contrast-enhancing tumor.
6. Patients who elect to have Optune therapy (Tumor Treating Fields) are not eligible to participate in this trial.
7. Patient has had non-standard radiation therapy for glioblastoma (i.e., whole brain radiation therapy, gamma knife or LINAC stereotactic radiosurgery).
8. Prior or concurrent immunotherapy for brain tumor, including immune checkpoint inhibitors (pembrolizumab, nivolumab or ipilimumab) or other cancer vaccine therapy.
9. Prior or concurrent treatment with bevacizumab.
10. Patients with serious concurrent infection or medical illness, which in the treating physician's opinion would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety.
11. History of tuberculosis or other granulomatous disease.
12. Patient is pregnant or breast-feeding.
13. Patient has received any other chemotherapeutic agent or investigational drug in addition to standard of care radiation therapy with concomitant temozolomide (chemoradiation per Stupp protocol).
14. Patient with concurrent or prior malignancy is ineligible unless he or she has had curatively treated carcinoma-in-situ or basal cell carcinoma of the skin.
15. Patients who have had repeat craniotomy for tumor therapy after receiving RT and TMZ treatment (i.e., chemoradiation).
16. Patients who have had surgical implantation of carmustine (Gliadel) wafers are not eligible to participate in this study.
17. Known history of systemic autoimmune disorder.
18. Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency syndrome (AIDS) related illness or other serious medical illness.
19. Patient has a contraindication to MRI scans or to gadolinium contrast agent.
20. Patient has a contraindication to temozolomide.
21. Patient is unwilling or unable to follow protocol requirements.
22. Patient has received any other investigational treatment for the glioblastoma.
23. Any condition which in the Investigator's opinion makes the candidate unsuitable to receive the study drug or protocol procedures.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Translational Drug Development
OTHER
Merit
UNKNOWN
MimiVax, LLC
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Robert Fenstermaker, MD
Role: PRINCIPAL_INVESTIGATOR
Chief Medical Officer
Michael Ciesielski, PhD
Role: STUDY_DIRECTOR
Chief Executive Officer
Manmeet S Ahluwalia, MD, MBA
Role: PRINCIPAL_INVESTIGATOR
Study Principal Investigator
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of California
San Francisco, California, United States
Miami Cancer Institute
Miami, Florida, United States
Norton Cancer Center
Louisville, Kentucky, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Atlantic Health
Summit, New Jersey, United States
Roswell Park Comprehensive Cancer Center
Buffalo, New York, United States
NYU Langone Health
New York, New York, United States
Northwell
New York, New York, United States
Cleveland Clinic
Cleveland, Ohio, United States
Texas Oncology
Austin, Texas, United States
Fred Hutchinson Cancer Center (FHCC)
Seattle, Washington, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.
Ciesielski MJ, Ahluwalia MS, Munich SA, Orton M, Barone T, Chanan-Khan A, Fenstermaker RA. Antitumor cytotoxic T-cell response induced by a survivin peptide mimic. Cancer Immunol Immunother. 2010 Aug;59(8):1211-21. doi: 10.1007/s00262-010-0845-x. Epub 2010 Apr 27.
Andersen MH, Pedersen LO, Becker JC, Straten PT. Identification of a cytotoxic T lymphocyte response to the apoptosis inhibitor protein survivin in cancer patients. Cancer Res. 2001 Feb 1;61(3):869-72.
Hadrup SR, Gehl J, Sorensen RB, Geertsen PF, Straten PT, Andersen MH. Persistence of survivin specific T cells for seven years in a melanoma patient during complete remission. Cancer Biol Ther. 2006 May;5(5):480-2. doi: 10.4161/cbt.5.5.2652. Epub 2006 May 5.
Baxevanis CN, Voutsas IF, Tsitsilonis OE, Gritzapis AD, Sotiriadou R, Papamichail M. Tumor-specific CD4+ T lymphocytes from cancer patients are required for optimal induction of cytotoxic T cells against the autologous tumor. J Immunol. 2000 Apr 1;164(7):3902-12. doi: 10.4049/jimmunol.164.7.3902.
Moeller M, Kershaw MH, Cameron R, Westwood JA, Trapani JA, Smyth MJ, Darcy PK. Sustained antigen-specific antitumor recall response mediated by gene-modified CD4+ T helper-1 and CD8+ T cells. Cancer Res. 2007 Dec 1;67(23):11428-37. doi: 10.1158/0008-5472.CAN-07-1141.
Yu J, Ren X, Cao S, Zhang W, Hao X. Th1 polarization and apoptosis-inducing activity of CD4+ T -cells in cytokine-induced killers might favor the antitumor cytotoxicity of cytokine-induced killers in vivo. Cancer Biother Radiopharm. 2006 Jun;21(3):276-84. doi: 10.1089/cbr.2006.21.276.
Surman DR, Dudley ME, Overwijk WW, Restifo NP. Cutting edge: CD4+ T cell control of CD8+ T cell reactivity to a model tumor antigen. J Immunol. 2000 Jan 15;164(2):562-5. doi: 10.4049/jimmunol.164.2.562.
Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll D, Levitsky H. The central role of CD4(+) T cells in the antitumor immune response. J Exp Med. 1998 Dec 21;188(12):2357-68. doi: 10.1084/jem.188.12.2357.
Pardoll DM. Inducing autoimmune disease to treat cancer. Proc Natl Acad Sci U S A. 1999 May 11;96(10):5340-2. doi: 10.1073/pnas.96.10.5340. No abstract available.
Fenstermaker RA, Figel SA, Qiu J, Barone TA, Dharma SS, Winograd EK, Galbo PM, Wiltsie LM, Ciesielski MJ. Survivin Monoclonal Antibodies Detect Survivin Cell Surface Expression and Inhibit Tumor Growth In Vivo. Clin Cancer Res. 2018 Jun 1;24(11):2642-2652. doi: 10.1158/1078-0432.CCR-17-2778. Epub 2018 Mar 14.
Rohayem J, Diestelkoetter P, Weigle B, Oehmichen A, Schmitz M, Mehlhorn J, Conrad K, Rieber EP. Antibody response to the tumor-associated inhibitor of apoptosis protein survivin in cancer patients. Cancer Res. 2000 Apr 1;60(7):1815-7.
Fenstermaker RA, Ciesielski MJ, Qiu J, Yang N, Frank CL, Lee KP, Mechtler LR, Belal A, Ahluwalia MS, Hutson AD. Clinical study of a survivin long peptide vaccine (SurVaxM) in patients with recurrent malignant glioma. Cancer Immunol Immunother. 2016 Nov;65(11):1339-1352. doi: 10.1007/s00262-016-1890-x. Epub 2016 Aug 30.
Adida C, Crotty PL, McGrath J, Berrebi D, Diebold J, Altieri DC. Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. Am J Pathol. 1998 Jan;152(1):43-9.
Sasaki T, Lopes MB, Hankins GR, Helm GA. Expression of survivin, an inhibitor of apoptosis protein, in tumors of the nervous system. Acta Neuropathol. 2002 Jul;104(1):105-9. doi: 10.1007/s00401-002-0532-x. Epub 2002 Mar 29.
Fukuda S, Pelus LM. Survivin, a cancer target with an emerging role in normal adult tissues. Mol Cancer Ther. 2006 May;5(5):1087-98. doi: 10.1158/1535-7163.MCT-05-0375.
Zaffaroni N, Daidone MG. Survivin expression and resistance to anticancer treatments: perspectives for new therapeutic interventions. Drug Resist Updat. 2002 Apr;5(2):65-72. doi: 10.1016/s1368-7646(02)00049-3.
Luoto S, Hermelo I, Vuorinen EM, Hannus P, Kesseli J, Nykter M, Granberg KJ. Computational Characterization of Suppressive Immune Microenvironments in Glioblastoma. Cancer Res. 2018 Oct 1;78(19):5574-5585. doi: 10.1158/0008-5472.CAN-17-3714. Epub 2018 Jun 19.
Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010 Apr 10;28(11):1963-72. doi: 10.1200/JCO.2009.26.3541. Epub 2010 Mar 15.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
I-813720
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.