SurVaxM Plus Adjuvant Temozolomide for Newly Diagnosed Glioblastoma (SURVIVE)

NCT05163080 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: I-813720
• Study Type: interventional
• Target: 247
• Locations: 1 country
• Sites: 11

Brief Summary

The main purpose of this study is to determine whether adding SurVaxM to standard-of-care temozolomide chemotherapy is better than temozolomide treatment alone for patients with newly diagnosed glioblastoma. This study is designed to compare the length of survival in patients with newly diagnosed glioblastoma who receive temozolomide plus SurVaxM to that of patients treated with standard-of-care temozolomide plus placebo. This study aims to discover what effects, both good and bad, this combination of drugs may have on you and to see if the study drug (SurVaxM) can create an immune response in your blood that is directed against your cancer cells. This study also aims to determine whether treatment with SurVaxM plus temozolomide improves the survival of glioblastoma patients like yourself compared to treatment with temozolomide alone.

Conditions

Newly Diagnosed Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  To compare overall survival (OS) in patients with newly diagnosed glioblastoma between treatment arms A \& B

  36 Months

Secondary Outcomes (4)

• Grade 3 & Grade 4 Toxicities

  36 Months

• Progression Free Survival Comparison

  36 months

• Overall Survival at Specified Time Points

  24 months

• Progression-Free Survival at specific time points

  12 months

Other Outcomes (3)

• Predictive Value of perfusion-weighted imaging - pseudo-progression

  36 months

• Objective Image Based Tumor Response Rate

  36 months

• Evaluate molecular predictors of response to SurVaxM

  36 months

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Peptide Vaccine (SurVaxM) in emulsion with Montanide given together with locally administered Sargramostim plus adjuvant oral Temozolomide

Biological: SurVaxM

Arm B

PLACEBO COMPARATOR

Saline-Montanide emulsion with locally administered saline (instead of sargramostim) plus adjuvant oral temozolomide

Biological: SurVaxM

Interventions

SurVaxM BIOLOGICAL

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 A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be included in this study, participants must meet the following criteria:
• Age ≥ 18 years of age.
• 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).
• Pathologically confirmed diagnosis of glioblastoma of the cerebrum.
• The result of tumor MGMT methylation study must be available.
• The result of tumor IDH-1 mutation test must be available.
• \. Have the following clinical laboratory values obtained within 14 days prior to registration:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Hemoglobin (Hgb) ≥ 9.0 g/dL
• Total bilirubin: ≤ 1.5 x ULN
• ALT and AST ≤ 4.0 x ULN
• Creatinine ≤ 1.8 mg/dL
• Prothrombin time (PT) within 1.5x normal limits
• Activated partial thromboplastin time (aPPT) within 1.5x control

You may not qualify if:

• Participants with any of the following will be excluded from this study:
• Recurrent or progressive glioblastoma.
• Gliosarcoma, anaplastic astrocytoma, oligodendroglioma, ependymoma, low grade glioma or any histology other than glioblastoma.
• Multicentric glioblastoma or glioblastoma involving the brainstem or cerebellum, or leptomeningeal or spinal extension present at diagnosis.
• Residual contrast enhancement \> 1 cm3 on post-operative scan obtained within 72 hours of surgery.
• Absence of MRI obtained within 72 hours of craniotomy documenting
• ≤ 1 cm3 contrast-enhancing tumor.
• Patients who elect to have Optune therapy (Tumor Treating Fields) are not eligible to participate in this trial.
• Patient has had non-standard radiation therapy for glioblastoma (i.e., whole brain radiation therapy, gamma knife or LINAC stereotactic radiosurgery).
• Prior or concurrent immunotherapy for brain tumor, including immune checkpoint inhibitors (pembrolizumab, nivolumab or ipilimumab) or other cancer vaccine therapy.
• Prior or concurrent treatment with bevacizumab.
• 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.
• History of tuberculosis or other granulomatous disease.
• Patient is pregnant or breast-feeding.
• 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).

Sponsors & Collaborators

• MimiVax, LLC: lead
• Translational Drug Development: collaborator
• Merit: collaborator

Study Sites (11)

University of California

San Francisco, California, 94143, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Norton Cancer Center

Louisville, Kentucky, 40241, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Atlantic Health

Summit, New Jersey, 07960, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Northwell

New York, New York, 10075, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Texas Oncology

Austin, Texas, 78705, United States

Location

Fred Hutchinson Cancer Center (FHCC)

Seattle, Washington, 98109, United States

Location

Related Publications (19)

• 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.

  PMID: 15758009 RESULT

• 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.

  PMID: 20422411 RESULT

• 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.

  PMID: 11221872 RESULT

• 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.

  PMID: 16582593 RESULT

• 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.

  PMID: 10725753 RESULT

• 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.

  PMID: 18056471 RESULT

• 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.

  PMID: 16918305 RESULT

• 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.

  PMID: 10623795 RESULT

• 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.

  PMID: 9858522 RESULT

• 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.

  PMID: 10318881 RESULT

• 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.

  PMID: 29540489 RESULT

• 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.

  PMID: 10766164 RESULT

• 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.

  PMID: 27576783 RESULT

• 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.

  PMID: 9422522 RESULT

• 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.

  PMID: 12070671 RESULT

• 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.

  PMID: 16731740 RESULT

• 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.

  PMID: 12135582 RESULT

• 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.

  PMID: 29921698 RESULT

• 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.

  PMID: 20231676 RESULT

Study Officials

• Robert Fenstermaker, MD

  Chief Medical Officer

  PRINCIPAL INVESTIGATOR

• Michael Ciesielski, PhD

  Chief Executive Officer

  STUDY DIRECTOR

• Manmeet S Ahluwalia, MD, MBA

  Study Principal Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a prospective, randomized, placebo-controlled, multi-center study of patients with newly diagnosed Glioblastoma (nGBM)to evaluate a peptide vaccine (SurVaxM) in emulsion with Montanide given together with locally administered sargramostim plus adjuvant oral temozolomide (Arm A) versus saline-Montanide emulsion with locally administered saline (instead of sargramostim) plus adjuvant oral temozolomide (Arm B)

Study Record Dates

• First Submitted: December 6, 2021
• First Posted: December 20, 2021
• Study Start: November 18, 2021
• Primary Completion: August 18, 2024
• Study Completion: August 18, 2024
• Last Updated: February 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)