Vaccine Therapy + Temozolomide for Glioblastoma

Not currently recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Roswell Park Cancer Institute

Must be taking: Temozolomide

Must not be taking: Immunotherapy, Other chemotherapeutics

Disqualifiers: Pregnancy, Autoimmune disorder, HIV/AIDS, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a vaccine therapy (SVN53-67/M57-KLH Peptide Vaccine) combined with the chemotherapy drug temozolomide for individuals with newly diagnosed glioblastoma, an aggressive brain cancer. The vaccine aims to trigger the immune system to attack cancer cells, while temozolomide stops these cells from growing and spreading. Researchers seek to determine if the combination is more effective than temozolomide alone. Suitable participants have a confirmed glioblastoma diagnosis and have completed initial radiation and chemotherapy treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot receive other treatments for your tumor besides temozolomide, and you must not have received any immunotherapy for your brain tumor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the SVN53-67/M57-KLH peptide vaccine, known as SurVaxM, is generally safe and well-tolerated. In previous studies, patients with recurring or worsening malignant glioma (a type of brain tumor) received this vaccine without major safety concerns. These studies reported no serious side effects directly linked to the vaccine.

Temozolomide, a chemotherapy drug approved by the FDA for treating glioblastoma, is generally considered safe, especially when used as an additional treatment after radiation. Some side effects, such as low blood cell counts, can occur but are usually manageable.

Overall, these findings suggest that both the vaccine and temozolomide are relatively safe for patients, though monitoring for side effects remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for glioblastoma, which typically involve surgery, radiation, and the chemotherapy drug temozolomide, the investigational treatment in this trial includes a vaccine called SVN53-67/M57-KLH. This vaccine is designed to stimulate the immune system to specifically target and attack glioblastoma cells, potentially offering a more targeted approach. Researchers are excited about this treatment because it combines the established efficacy of temozolomide with the innovative potential of an immune-based therapy, which could lead to improved outcomes for patients with this aggressive brain cancer. This combination aims to enhance the body's natural defenses against the tumor, providing a novel and promising strategy in the fight against glioblastoma.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

In this trial, participants will receive a combination of the SurVaxM vaccine and the chemotherapy drug temozolomide to treat glioblastoma, a type of brain cancer. Research has shown that patients who received SurVaxM lived for a median of 21.8 months, with 26% surviving for three years, surpassing past results. SurVaxM helps the immune system attack cancer cells without causing major side effects. Temozolomide, a common chemotherapy drug, improves survival when combined with radiation therapy. Together, these treatments might offer a more effective way to fight glioblastoma. ^{1 2 5 6 7}

Who Is on the Research Team?

Robert Fenstermaker

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with newly diagnosed glioblastoma who've had surgery and chemotherapy with temozolomide, without disease progression. They must have a specific immune system type (HLA-A*02, A*03, A*11 or A*24), good kidney function, no serious bleeding risks or infections, not be pregnant or breastfeeding, and agree to use contraception.

Inclusion Criteria

Hemoglobin (Hgb) > 9.0 g/dL

My MRI after surgery shows no large remaining cancer areas.

Participants of child-bearing potential 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

Exclusion Criteria

I have not had cancer in the last 3 years, except for treated skin cancer or carcinoma-in-situ.

I am currently on cancer treatment other than temozolomide.

Patients who are pregnant or breast-feeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccine Priming

Participants receive the first priming dose of SVN53-67/M57-KLH peptide vaccine and sargramostim subcutaneously every 2 weeks for a total of 4 doses

8 weeks

4 visits (in-person)

Adjuvant Treatment

Participants receive standard adjuvant temozolomide orally or intravenously on days 1-5, repeating every 28 days for 6 courses or more, and SVN53-67/M57-KLH peptide vaccine every 12 weeks

24 weeks or more

6 visits (in-person) for temozolomide, additional visits for vaccine

Maintenance

Participants may receive maintenance SVN53-67/M57-KLH peptide vaccine every 12 weeks in the absence of disease progression or unacceptable toxicity

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SVN53-67/M57-KLH Peptide Vaccine
• Temozolomide

Trial Overview The study tests if adding a survivin peptide vaccine (SurVaxM) to the standard treatment of temozolomide improves outcomes in glioblastoma patients. The vaccine aims to help the body's immune system attack tumor cells that express survivin—a protein found in cancer cells.

How Is the Trial Designed?

Group I: Treatment (SurVaxM, temozolomide) Experimental Treatment 5 Interventions

Patients receive the first priming dose of SVN53-67/M57-KLH peptide vaccine in emulsion with montanide ISA 51 SC and sargramostim SC within 7-28 days after completion of chemoradiation. Treatment repeats every 2 weeks for a total of 4 doses in the vaccine priming phase and then every 12 weeks during the adjuvant phase in the absence of disease progression or unacceptable toxicity. Patients also receive standard adjuvant temozolomide PO or IV on days 1-5. Treatment repeats every 28 days for 6 courses or more (at the discretion of the investigator) in the absence of disease progression or unacceptable toxicity. Patients may then receive maintenance SVN53-67/M57-KLH peptide vaccine in emulsion with montanide ISA 51 SC and sargramostim SC every 12 weeks in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Published Research Related to This Trial

Rindopepimut, a peptide vaccine targeting the EGFRvIII mutation found in 20-30% of glioblastoma multiforme (GBM) cases, has shown significantly improved progression-free and overall survival rates in patients, making it a promising treatment option.

The vaccine has minimal side effects, primarily hypersensitivity reactions, indicating a favorable safety profile compared to current non-specific therapies for GBM, which often result in toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rindopepimut: an evidence-based review of its therapeutic potential in the treatment of EGFRvIII-positive glioblastoma. Babu, R., Adamson, DC.[2021]

In a Phase 2 study involving patients with recurrent glioblastoma, the multi-epitope long peptide vaccine TAS0313 showed an objective response rate of 11.1% and a disease control rate of 44.4%, indicating some efficacy in this challenging cancer.

TAS0313 was found to have an acceptable safety profile, with common side effects including injection site reactions and fever, but no severe adverse events or deaths reported during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the efficacy and safety of TAS0313 in adults with recurrent glioblastoma. Narita, Y., Okita, Y., Arakawa, Y.[2022]

The experimental EGFRvIII-targeted peptide vaccine successfully induced immune responses in patients with glioblastoma multiforme (GBM) undergoing treatment with temozolomide (TMZ), even in the presence of chemotherapy-induced lymphopenia.

Patients receiving the dose-intensified TMZ regimen showed greater immune responses and significantly improved median progression-free survival (15.2 months) and overall survival (23.6 months) compared to historical controls, indicating the vaccine's efficacy in targeting tumor cells without causing autoimmunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma. Sampson, JH., Aldape, KD., Archer, GE., et al.[2022]

The SurVaxM vaccine, targeting the survivin protein, was well tolerated in recurrent malignant glioma patients, with mostly mild side effects and no serious adverse events, indicating a favorable safety profile.

Immunologically, the vaccine successfully elicited immune responses in six out of eight evaluable patients, and showed promising clinical outcomes, with some patients maintaining stable disease for over 6 months and a median overall survival of 86.6 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical study of a survivin long peptide vaccine (SurVaxM) in patients with recurrent malignant glioma. Fenstermaker, RA., Ciesielski, MJ., Qiu, J., et al.[2023]

The survivin peptide mimic SVN53-67/M57 has been shown to induce a stronger antitumor immune response in mice with gliomas compared to the original SVN53-67 peptide, suggesting its potential as a more effective cancer vaccine.

SVN53-67/M57 demonstrated significantly higher binding affinity to the human HLA-A*0201 antigen, leading to enhanced cytotoxic T lymphocyte (CTL) responses against malignant glioma and primary central nervous system lymphoma cells, indicating its promise for cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor cytotoxic T-cell response induced by a survivin peptide mimic. Ciesielski, MJ., Ahluwalia, MS., Munich, SA., et al.[2021]

SurVaxM, a peptide vaccine targeting the survivin protein in glioblastoma cells, was found to be safe and well tolerated in a phase IIa trial with 64 patients, showing no serious adverse events related to the vaccine.

The combination of SurVaxM with adjuvant temozolomide (TMZ) resulted in a high progression-free survival rate of 95.2% at 6 months and a median overall survival of 25.9 months, indicating promising efficacy in treating newly diagnosed glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IIa Study of SurVaxM Plus Adjuvant Temozolomide for Newly Diagnosed Glioblastoma. Ahluwalia, MS., Reardon, DA., Abad, AP., et al.[2023]

Citations

1. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/57/NCT02455557/Prot_SAP_000.pdf

A Phase II Study of the Safety and Efficacy of SVN53-67/ ... This study demonstrated that: 1) the combination of temozolomide and. SurVaxM while not synergistic, was not detrimental to immunization ...

2. dana-farber.org dana-farber.org/clinical-trials/16-138

A Phase II Study fo the Safety and Efficacy of SVN53-67 ... This phase II trial studies the side effects and how well vaccine therapy works when given together with temozolomide in treating patients with newly ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12166567/

Recent developments in peptide vaccines against ... The trial achieved a mOS of 21.8 months and a 3-year survival rate of 26%, demonstrating extended survival compared to historical controls and ...

4. mimivax.com mimivax.com/wp-content/uploads/2019/10/ASCO-2019-SurVaxM-Phase-2-Poster.pdf

SurVaxM with standard therapy in newly diagnosed ... Conclusions: SurVaxM immunotherapy generated encouraging efficacy and immunogenicity in nGBM and has minimal toxicity. A randomized, prospective trial of ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/cam4.71187

Promising Cancer Vaccine for Glioblastoma Therapy: A ... TSA's cancer vaccines have shown encouraging early results; nevertheless, a meaningful comparison between neoantigen and TAA vaccines is impeded ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05163080

NCT05163080 | SurVaxM Plus Adjuvant Temozolomide for ... 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 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4218258/

IT-09: PHASE I STUDY OF SAFETY, TOLERABILITY AND ... This study demonstrated the safety and tolerability of SurVaxM in patients with recurrent or progressive malignant glioma following failure of standard therapy.