Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Amino Acids

Molgramostim

Sargramostim

Vaccines

Temozolomide

Carbamide Peroxide

Monatide (IMS 3015)

Keyhole-limpet hemocyanin

BIRC5 protein, human

Cysteine

Methionine

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

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

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).

SurVaxM

Robert Fenstermaker, MD

Michael Ciesielski, PhD

Manmeet S Ahluwalia, MD, MBA

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.

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.

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)

SurVaxM Plus Adjuvant Temozolomide for Newly Diagnosed Glioblastoma (SURVIVE)

Prospective Randomized Placebo-Controlled Trial of SurVaxM Plus Adjuvant Temozolomide for Newly Diagnosed Glioblastoma (SURVIVE)

To evaluate the predictive value of perfusion-weighted imaging in assessing pseudo-progression and post-vaccination enhancement in patents receiving SurVaxM

To evaluate the objective image based tumor response rate (applicable only for patients with valuable disease at study entry as defined by RANO criteria)

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

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

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

To compare Progression Free Survival in patients with newly diagnosed glioblastoma between treatment arms A \& B.

To compare treatment-associated OS at pre-specified time points (OS-15, OS-18, and OS-24) between treatment arms A \& B.

To compare treatment associated PFS at pre-specified time points (PFS-3, PFS-6, PFS-12) between treatment arms A \& B

Translational Drug Development

Merit

MimiVax, LLC

Nervous System Diseases

Medulloblastoma

Diffuse Intrinsic Pontine Glioma

Ependymoma

Oligodendroglioma

Brain Stem Neoplasms

Infratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Anaplastic Ependymoma

500 mcg (1 mL) SurVaxM emulsion with Montanide ISA 51. Sargramostim dose is 3.33 mcg/kg/dose for patients \< 30 kg, and 100 mcg for patients ≥ 30 kg.

Priming Phase: patients will get one dose of SurVaxM combined with Montanide ISA 51 through a subcutaneous injection at the start of the study and every 2 weeks for 6 weeks (for a total of 4 doses). At each SurVaxM/Montanide ISA 51 injection, patients will also get an injection of sargramostim.

Maintenance Phase: the patient will get a SurVaxM/Montanide ISA 51 dose along with a sargramostim dose about every 8 weeks for up to two years.

After finishing study treatment, patients will be followed for up to 3 years following the last dose of SurVaxM/Montanide ISA 51. Patients will be followed in clinic every 3 months during the follow-up.

500 mcg (1 mL) SurVaxM emulsion with Montanide ISA 51. Sargramostim dose is 3.33 mcg/kg/dose for patients \< 30 kg, and 100 mcg for patients ≥ 30 kg.

SurVaxM for patients with relapsed or progressive MB, HGG or ependymoma ages ≥10 and ≤21 years

SurVaxM for patients with relapsed or progressive MB, HGG or ependymoma ages ≥1 and <10 years

SurVaxM for patients with non-relapsed DIPG post radiation-therapy ages ≥1 and ≤21 years

Anneliese Rosdil, MSN

Nina Butingan, MBS

Nathan Robison, MD

Sonia Partap, MD, MS

Cynthia Campen, MD

Eugene Hwang, MD

Elias Sayour, MD

Jennifer King, RN

Jason Fangusaro, MD

Alicia Lenzen, MD

Clare Twist

Ira Dunkel, MD

Natasha Pillay Smiley, DO

James Felker, MD

Patricia Baxter, MD

Vijay Ramaswamy, MD

Aiman Siddiqi

Clare Twist, MD

Patients will receive a vaccine called SurVaxM on this study. While vaccines are usually thought of as ways to prevent diseases, vaccines can also be used to treat cancer. SurVaxM is designed to tell the body's immune system to look for tumor cells that express a protein called survivin and destroy them. The survivin protein can be found on up to 95% of glioblastomas and other types of cancer but is not found in normal cells. If the body's immune system knows to destroy cells that express survivin, it may help to control tumor growth and recurrence.

SurVaxM will be mixed with Montanide ISA 51 before it is given. Montanide ISA 51 is an ingredient that helps create a stronger immune response in people, which helps the vaccine work better.

This study has two phases: Priming and Maintenance. During the Priming Phase, patients will get one dose of SurVaxM combined with Montanide ISA 51 through a subcutaneous injection (a shot under the skin) at the start of the study and every 2 weeks for 6 weeks (for a total of 4 doses). At the same time that patients get the SurVaxM/Montanide ISA 51 injection, they will also get a second subcutaneous injection of a medicine called sargramostim. Sargramostim is given close to the SurVaxM//Montanide ISA 51 injection and works to stimulate the immune system to help the SurVaxM/Montanide ISA 51 work more effectively.

If a patient completes the Priming Phase without severe side effects and his or her disease stays the same or improves, he or she can continue to the Maintenance Phase. During the Maintenance Phase, the patient will get a SurVaxM/Montanide ISA 51 dose along with a sargramostim dose about every 8 weeks for up to two years.

After a patient finishes the study treatment, the doctor and study team will continue to follow his/her condition and watch for side effects up to 3 years following the last dose of SurVaxM/Montanide ISA 51. Patients will be seen in clinic every 3 months during the follow-up period.

This is a multicenter pilot study of SurVaxM (SVN53-67/M57-KLH) for children and young adults with progressive or relapsed medulloblastoma, high grade glioma, ependymoma and newly diagnosed diffuse intrinsic pontine glioma.

Survivin (BIRC5) is an inhibitor of apoptosis (IAP) protein that is highly expressed in many cancers. Survivin's high level of expression in certain pediatric malignancies makes it an attractive molecular target for new therapies, including active specific vaccination-based immunotherapy.

The design of the SurVaxM vaccine employs several strategies to create an effective antitumor immunogen, including: 1) incorporation of multiple MHC class I epitopes, 2) peptide modification to enhance binding to certain MHC class I molecules, 3) cytokine helper support, and 4) antibody-mediated tumor cell killing. All of these effects would not be expected with the unmodified class-I restricted short survivin peptides employed in previously studied glioma vaccines.

There are no prior clinical trials of SurVaxM in pediatric patients; however, SurVaxM has been studied in several adult trials, including a phase I study conducted at Roswell Park Comprehensive Cancer Center. Following the single-institution phase I trial, a multicenter phase IIa trial (NCT024455557) was conducted in 63 patients with newly diagnosed glioblastoma. All patients in this study underwent surgical resection of their tumors. Patients then underwent chemoradiation with temozolomide according to the Stupp protocol. This was followed by a one-month hiatus from chemotherapy, during which priming doses of SurVaxM were initiated. The priming phase of vaccination was then followed by initiation of standard adjuvant chemotherapy with temozolomide and maintenance doses of SurVaxM as an add-on to standard chemotherapy. There have been no regimen-limiting toxicities (RLT) or grade ≥ 3 SAE attributable to SurVaxM, with most toxicities being related to temozolomide. The most common AE was grade 1-2 injection site reaction with 2 patients experiencing Montanide-related granulomatous panniculitis with local skin ulceration at vaccine injection sites, both of which resolved. Humoral and survivin-specific CD8+ T cell responses were observed in almost all patients. Twelve-month overall survival (OS12) was 86% from first immunization and 93.4% from diagnosis. OS12 for meMGMT was 93.1% and unMGMT was 78% from first immunization. Median time to tumor progression (mPFS) was 13.9 months from diagnosis. Although not a randomized trial, these results are superior to overall survival reported in various studies in which patients received standard of care treatment for this disease. A randomized phase IIb clinical trial of standard therapy plus SurVaxM is currently being developed with intent for drug registration, if successful.

The primary objective of this trial is to assess the toxicity profile of SurVaxM in emulsion with Montanide plus sargramostim in children with relapsed or progressive medulloblastoma and high-grade glioma, ependymoma and non-recurrent diffuse intrinsic pontine glioma post-radiation therapy. Patients will be enrolled into three separate strata based on age and diagnosis. Enrollment will be staged to allow for safety evaluations between strata.

Each patient will receive 500 micrograms SurVaxM as a 1:1 mixture with Montanide ISA 51 in a water-in-oil emulsion. The SurVaxM-Montanide emulsion injection will be followed immediately by sargramostim (or biosimilar) given via a second separate subcutaneous injection in close proximity to the vaccine injection site. Patients will receive four injections administered over a 6-week period, followed by 14 days of follow-up, called the Priming Phase (8 weeks total). Beginning 8 weeks after the fourth priming dose, a maintenance dose of SurVaxM with Montanide ISA 51 may be given every 8 weeks (± 2 weeks) for two years or until an off-treatment criterion is met.

All participants receive the same intervention/treatment in disease specific or age stratified fashion.

A Pilot Study of SurVaxM in Children Progressive or Relapsed Medulloblastoma, High Grade Glioma, Ependymoma and Newly Diagnosed Diffuse Intrinsic Pontine Glioma

A Pilot Study of Safety, Tolerability, and Immunological Effects of SurVaxM in Pediatric Patients With Progressive or Relapsed Medulloblastoma, High Grade Glioma, Ependymoma and Newly Diagnosed Diffuse Intrinsic Pontine Glioma

The Pediatric Brain Tumor Consortium (PBTC) ensures that high dimensional molecular data generated from PBTC samples will be submitted to the NIH Database of Genotypes and Phenotypes (dbGaP) or other NIH-designated data repository. PBTC is required to make data available to other investigators for use in research projects. An investigator requesting data from published PBTC studies will submit a proposal describing the studies from which data are requested, the requested data, and a list of investigators in the project and their affiliated institutions, along with the investigator's CV to the PBTC Steering Committee for review. Once approved, the requesting investigator will be asked to complete a Data Transfer Agreement before the release of deidentified data. Requests for data are typically only considered once the primary study manuscript has been published though exceptions may be made in the event of long delays in the primary study data publication.

Overall response assessment takes into account response (complete response, partial response, stable disease, progressive disease) in both target and non-target lesion, and the appearance of new lesions, where applicable, according to the criteria described in the protocol. Best radiographic response observed while on treatment will be reported for each patient and percentage of patients that fall in each response category will be reported.

Interval of time between date of initiation of protocol treatment and minimum date of documentation of Progressive Disease

Time between date of initiation of protocol treatment and minimum date of death due to any cause or date of last follow-up.

The RLT rate during the first 8 weeks (14 days after the 4th priming dose of vaccine) will be used as the primary endpoint for safety monitoring and for determining when enrollment can begin in the next sub-cohort.

A separate RLT assessment window for risk of pseudoprogression will encompass the 6 weeks for administration of 4 priming doses + 8 weeks of follow-up after administration of the 4th priming dose. Pseudoprogression RLTs during this interval will be included in the primary safety monitoring rules and analysis.

Differences in estimated rCBV and ktrans values between patients with pseudoprogression vs. true progression will be reported.

Roswell Park Cancer Institute

National Cancer Institute (NCI)

American Lebanese Syrian Associated Charities (ALSAC)

Pediatric Brain Tumor Consortium

Symptoms and General Pathology

Recurrence

Disease Attributes

Pembrolizumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Immunologic Factors

Adjuvants, Immunologic

Arm A is patients with first recurrence of glioblastoma who have failed prior chemotherapy and radiation but have not received any immunotherapy.

Arm B is an exploratory arm of 10 patients who have failed prior anti-PD1 therapy.

500 mcg per dose, dosed every two weeks for 4 doses and then every 3 months

100 mcg per dose, dosed every two weeks for 4 doses and then every 3 months

1 ml per dose dosed every two weeks for 4 doses and then every 3 months

Montanide ISA 51

David Peereboom, MD

The main purpose of this study is to assess the clinical activity of Pembrolizumab and SurVaxM in participants with recurrent glioblastoma.

Primary objective: Assess clinical activity of Pembrolizumab and SurVaxM in participants with recurrent glioblastoma using progression free survival at 6 months (PFS-6).

Secondary objective: : Assess safety and tolerability of Pembrolizumab and SurVaxM in participants with recurrent glioblastoma.

This is a Phase II study of two arms in participants with recurrent glioblastoma. Arm A will include participants with first recurrence of glioblastoma who have failed prior chemotherapy and radiation but have not received any immunotherapy. Arm B is an exploratory arm of 10 participants who have failed prior anti-PD1 therapy.

All patients will receive the study drug combination consisting of SurVaxM and pembrolizumab (PEM) with no randomization, stratification or dose escalation.

Study of Pembrolizumab Plus SurVaxM for Glioblastoma at First Recurrence

Phase II Study of Pembrolizumab Plus SurVaxM for Glioblastoma at First Recurrence

Will share main findings of the clinical study report (CSR)

Assess clinical activity of Pembrolizumab and SurVaxM in patients with recurrent glioblastoma using PFS at 6 months (PFS-6)

Safety and tolerability of Pembrolizumab and SurVaxM in patients with recurrent glioblastoma measured on ongoing basis with CTCAE v 5 grading as per NCI. Grade 1-2 and 3-5 events will be recorded and reported.

David Peereboom

Principal Investigator

Each participant will receive 4 doses of SVN53-67/M57-KLH (SurVaxM) spaced two weeks apart. This phase of treatment is known as the prime-boost phase and will take 6 weeks to complete. After completion of the prime-boost phase of treatment, the participant will receive a dose ofSVN53-67/M57-KLH (SurVaxM) every 3 months for up to two years

Ajay Abad, MD

Data from clinical trials suggest that SurVaxM administered as a single agent, or in combination with standard glioblastoma chemotherapy treatment regimens to patients with recurrent or newly diagnosed glioblastoma, is generally well tolerated and may increase progression free survival and overall survival in some patients

SurVaxM Expanded Access Protocol

Expanded Access to SurVaxM for Treatment of Patients With Glioblastoma Who Have No Access to Other Comparable or Alternative Therapy or Have Completed Treatment on a Non-Randomized Clinical Trial of SurVaxM and May Benefit From Further Treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
SurVaxM Plus Adjuvant Temozolomide for Newly Diagnosed Glioblastoma (SURVIVE)	NCT05163080	Newly Diagnosed...	SurVaxM	18 Years -	MimiVax, LLC
SurVaxM Plus Adjuvant Temozolomide for Newly Diagnosed Glioblastoma (SURVIVE)	NCT05163080	Newly Diagnosed...	SurVaxM	18 Years -	MimiVax, LLC
A Pilot Study of SurVaxM in Children Progressive or Relapsed Medulloblastoma, High Grade Glioma, Ependymoma and Newly Diagnosed Diffuse Intrinsic Pontine Glioma	NCT04978727	Medulloblastoma Glioblastoma Mu... Anaplastic Astr... High-grade Astr... Anaplastic Olig... Anaplastic Epen... Ependymoma Diffuse Intrins...	SurVaxM for pat... SurVaxM for pat... SurVaxM for pat...	1 Year - 21 Years	Pediatric Brain Tumor Consortium
Study of Pembrolizumab Plus SurVaxM for Glioblastoma at First Recurrence	NCT04013672	Recurrent Gliob...	Pembrolizumab SurVaxM Sargramostim Montanide ISA 5...	18 Years -	Case Comprehensive Cancer Center
SurVaxM Expanded Access Protocol	NCT04802447	Glioblastoma	SurVaxM	18 Years -	Roswell Park Cancer Institute
Study of Pembrolizumab Plus SurVaxM for Glioblastoma at First Recurrence	NCT04013672	Recurrent Gliob...	Pembrolizumab SurVaxM Sargramostim Montanide ISA 5...	18 Years -	Case Comprehensive Cancer Center

Spots Global Cancer Trial Database for survaxm

Every month we try and update this database with for survaxm cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for survaxm

Every month we try and update this database with for survaxm cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for survaxm cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.