Vaccine Therapy + Temozolomide for Glioblastoma

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

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies how well a special vaccine works with a common chemotherapy drug in treating patients with recently found brain cancer. The vaccine helps the immune system fight the cancer, while the chemotherapy attacks the cancer cells directly.

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 the combination of SurVaxM vaccine and Temozolomide safe for humans?

The combination of SurVaxM vaccine and Temozolomide has been studied for safety in patients with glioblastoma. SurVaxM was generally well tolerated, with mostly mild side effects like local injection site reactions and fatigue, and no serious side effects directly linked to the treatment. ^{1 2 3 4 5}

What makes the Vaccine Therapy + Temozolomide treatment unique for glioblastoma?

This treatment is unique because it combines SurVaxM, a vaccine that activates the immune system against survivin (a protein highly expressed by glioblastoma cells), with temozolomide, a chemotherapy drug. This combination aims to enhance the immune response while providing the standard chemotherapy benefits, potentially improving survival rates for patients with newly diagnosed glioblastoma. ^{1 2 4 6 7}

What data supports the effectiveness of the treatment Vaccine Therapy + Temozolomide for Glioblastoma?

Research shows that the SurVaxM vaccine, part of this treatment, can activate the immune system against glioblastoma cells, leading to immune responses and some patients experiencing stable disease for over 6 months. Additionally, the combination of SurVaxM with temozolomide has been studied for safety and survival benefits in patients with newly diagnosed glioblastoma. ^{1 2 3 4 5}

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

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

Participant 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

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

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]

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]

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]

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]

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]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Phase IIa Study of SurVaxM Plus Adjuvant Temozolomide for Newly Diagnosed Glioblastoma. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

A Cancer Research UK First Time in Human Phase I Trial of IMA950 (Novel Multipeptide Therapeutic Vaccine) in Patients with Newly Diagnosed Glioblastoma. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Antitumor cytotoxic T-cell response induced by a survivin peptide mimic. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Clinical study of a survivin long peptide vaccine (SurVaxM) in patients with recurrent malignant glioma. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of the efficacy and safety of TAS0313 in adults with recurrent glioblastoma. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

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