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Trial record 2 of 6 for:    survaxm

SurVaxM Plus Adjuvant Temozolomide for Newly Diagnosed Glioblastoma (SURVIVE) (SURVIVE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05163080
Recruitment Status : Recruiting
First Posted : December 20, 2021
Last Update Posted : April 28, 2022
Sponsor:
Collaborators:
Translational Drug Development
Imaging Endpoints
Information provided by (Responsible Party):
MimiVax, LLC

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.

Condition or disease Intervention/treatment Phase
Newly Diagnosed Glioblastoma Biological: SurVaxM Phase 2

Detailed Description:

This is a randomized, placebo-controlled study. That means that some patients will receive an active drug (SurVaxM) and some will receive an inactive drug (placebo). Patients who agree to participate will be randomized (chance) to one of two groups. Patients that are randomized by chance to receive SurVaxM will be treated with standard-of-care temozolomide plus an injection under the skin of SurVaxM in Montanide (a milky white substance that helps SurVaxM to be recognized by the patient's immune system). Patients in this group will also receive a second separate injection of a drug called sargramostim that boosts the patient's immune system at the site of the first injection. These injections will be repeated at regular intervals according to a schedule.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 265 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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)
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double-Blind
Primary Purpose: Treatment
Official Title: Prospective Randomized Placebo-Controlled Trial of SurVaxM Plus Adjuvant Temozolomide for Newly Diagnosed Glioblastoma (SURVIVE)
Actual Study Start Date : November 18, 2021
Estimated Primary Completion Date : August 18, 2023
Estimated Study Completion Date : April 18, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Arm A
Peptide Vaccine (SurVaxM) in emulsion with Montanide given together with locally administered Sargramostim plus adjuvant oral Temozolomide
Biological: 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).

Placebo Comparator: Arm B
Saline-Montanide emulsion with locally administered saline (instead of sargramostim) plus adjuvant oral temozolomide
Biological: 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).




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: 36 Months ]
    To compare overall survival (OS) in patients with newly diagnosed glioblastoma between treatment arms A & B


Secondary Outcome Measures :
  1. Grade 3 & Grade 4 Toxicities [ Time Frame: 36 Months ]
    To tabulate the number and type of Grade 3 & Grade 4 toxicities, according to the NCI Common Toxicity Criteria for Adverse Events (NCI CTCAEs) Version 5

  2. Progression Free Survival Comparison [ Time Frame: 36 months ]
    To compare Progression Free Survival in patients with newly diagnosed glioblastoma between treatment arms A & B.

  3. Overall Survival at Specified Time Points [ Time Frame: 24 months ]
    To compare treatment-associated OS at pre-specified time points (OS-15, OS-18, and OS-24) between treatment arms A & B.

  4. Progression-Free Survival at specific time points [ Time Frame: 12 months ]
    To compare treatment associated PFS at pre-specified time points (PFS-3, PFS-6, PFS-12) between treatment arms A & B


Other Outcome Measures:
  1. Predictive Value of perfusion-weighted imaging - pseudo-progression [ Time Frame: 36 months ]
    To evaluate the predictive value of perfusion-weighted imaging in assessing pseudo-progression and post-vaccination enhancement in patents receiving SurVaxM

  2. Objective Image Based Tumor Response Rate [ Time Frame: 36 months ]
    To evaluate the objective image based tumor response rate (applicable only for patients with valuable disease at study entry as defined by RANO criteria)

  3. Evaluate molecular predictors of response to SurVaxM [ Time Frame: 36 months ]
    To evaluate the molecular predictors of response to SurVaxM, including MGMT methylation status, anti-surviving immunoglobin titers, surviving-specific CD8+ responses, tumor survivin expression levels and other molecular tumor tissue markers



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

To be included in this study, participants must meet the following 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:

Participants with any of the following will be excluded from this study:

  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05163080


Contacts
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Contact: Danielle M Casucci, BS 7168614169 dcasucci@mimivax.com
Contact: Steve Norton, MBA, PhD 208.840.0119 snorton@td2inc.com

Locations
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United States, Kentucky
Norton Cancer Center Recruiting
Louisville, Kentucky, United States, 40241
Contact: Juanita Von Dwingelo    502-629-3681    Juanita.VonDwingelo@nortonhealthcare.org   
Principal Investigator: Renato LaRocca, MD         
Sub-Investigator: Lennea E Coombs, MHS, PA-C         
Sub-Investigator: Kaylyn Sinicrope, MD         
Sub-Investigator: Emily K Sturgeon, MSN, APRN         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: David Reardon, MD       David_Reardon@DFCI.Harvard.edu   
Contact: Corey Laforest-Roys       corey_laforest-roys@dfci.harvard.edu   
Sub-Investigator: Rameen Beroukhim, MD, PhD         
Sub-Investigator: Eudocia Quant Lee, MD, MPH         
Sub-Investigator: Ugonma Chukwueke, MD         
Sub-Investigator: Lakshmi Nayak, MD         
Sub-Investigator: Patrick Wen, MD         
Sub-Investigator: Jose R McFaline Figueroa, MD, PhD         
Sub-Investigator: Elisa Aquilanti, MD         
Sub-Investigator: Luis N Gonzalez Castro, MD, PhD         
Sub-Investigator: Tracy Batchelor, MD         
United States, New Jersey
Atlantic Health Recruiting
Summit, New Jersey, United States, 07960
Contact: Maridel Asuncion, RN       Maridel.Asuncion@atlantichealth.org   
Principal Investigator: Robert Aiken, MD         
United States, New York
Roswell Park Comprehensive Cancer Center Recruiting
Buffalo, New York, United States, 14263
Contact: Thao Uyen Dang, MS    716-845-1689    thaouyen.dang@roswellpark.org   
Principal Investigator: Ajay Abad, MD         
Sub-Investigator: Andrew Fabiano, MD         
Sub-Investigator: Chainazom Ibegbu, MD         
Sub-Investigator: Laszlo Metchler, MD         
NYU Langone Health Not yet recruiting
New York, New York, United States, 10016
Principal Investigator: Marissa Barbaro, MD         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Marci Ciolfi       Ciolfim@ccf.org   
Principal Investigator: David Peereboom, MD         
Sponsors and Collaborators
MimiVax, LLC
Translational Drug Development
Imaging Endpoints
Investigators
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Principal Investigator: Robert Fenstermaker, MD Chief Medical Officer
Study Director: Michael Ciesielski, PhD Chief Executive Officer
  Study Documents (Full-Text)

Documents provided by MimiVax, LLC:
Publications of Results:

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Responsible Party: MimiVax, LLC
ClinicalTrials.gov Identifier: NCT05163080    
Other Study ID Numbers: I-813720
First Posted: December 20, 2021    Key Record Dates
Last Update Posted: April 28, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue