Peptide Vaccine for Carcinoid Tumor

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Roswell Park Cancer Institute

Must be taking: Somatostatin analogues

Must not be taking: Systemic corticosteroids

Disqualifiers: Pregnancy, Autoimmune disorder, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

14 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects of survivin long peptide vaccine and how it works with the immune system in treating patients with neuroendocrine tumors that have spread to other parts of the body (metastatic). Tumor cells make proteins that are not usually produced by normal cells. The body sees these proteins as not belonging and sends white blood cells called T cells to attack the tumor cells that contain these proteins. By vaccinating with small pieces of these proteins called peptides, the immune system can be made to kill tumor cells. Giving survivin long peptide vaccine to patients who have survivin expression in their tumors may create an immune response in the blood that is directed against neuroendocrine tumors.

Do I need to stop my current medications to join the trial?

The trial allows patients to continue taking somatostatin analogues (SSA) while participating. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

What data supports the effectiveness of the treatment SVN53-67/M57-KLH Peptide Vaccine, SurVaxM, SVN53-67/M57-KLH Peptide Vaccine for carcinoid tumor?

Research shows that the SurVaxM vaccine, which targets the survivin protein found in many cancers, has been effective in stimulating an immune response and prolonging survival in patients with recurrent malignant glioma. This suggests potential effectiveness in other cancers, like carcinoid tumors, that express survivin. ^{1 2 3 4 5}

Is the SurVaxM (SVN53-67/M57-KLH Peptide Vaccine) safe for humans?

In a clinical study, the SurVaxM vaccine was generally well tolerated in patients with recurrent malignant glioma, with mostly mild side effects like local injection site reactions and fatigue. No serious adverse events were directly linked to the vaccine. ^{1 2 3 6 7}

What makes the SurVaxM peptide vaccine treatment unique for carcinoid tumors?

The SurVaxM peptide vaccine is unique because it targets survivin, a protein that helps cancer cells avoid death, and stimulates the immune system to attack tumors. This vaccine is designed to enhance both CD4+ and CD8+ T-cell responses, potentially offering a more robust immune attack against cancer cells compared to traditional treatments. ^{1 2 3 4 8}

Research Team

Renuka V. Iyer

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

This trial is for patients with metastatic neuroendocrine tumors of the gastrointestinal tract, pancreas, or lungs. Participants must have normal kidney function, be relatively independent in daily activities, and show tumor progression recently. They can continue somatostatin analogues if already using them and must not be at high risk of bleeding.

Inclusion Criteria

My neuroendocrine tumor tissue has tested positive for survivin.

I am on full-dose anticoagulants and meet specific criteria.

I am currently taking somatostatin analogues and can continue them during the study.

Exclusion Criteria

Received an investigational agent within 30 days prior to enrollment

Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SVN53-67/M57-KLH peptide vaccine and sargramostim subcutaneously every 2 weeks for up to 4 doses, and octreotide acetate intramuscularly every 28 days for 1 year

12 months

Bi-weekly visits for vaccine administration, monthly visits for octreotide

Extension

Participants who remain free of tumor progression at 6 months may receive additional doses of the vaccine and sargramostim every 3 months, for up to 1 year from the start of treatment

6-12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• SVN53-67/M57-KLH Peptide Vaccine

Trial Overview The trial tests a survivin long peptide vaccine combined with immune system boosters to see if it can trigger the body's defense against tumor cells that produce abnormal proteins. It's for those whose tumors express survivin and aims to create an immune response targeting these cancer cells.

Participant Groups

Group I: Treatment (SVN53-67/M57-KLH peptide vaccine, octreotide) Experimental Treatment 4 Interventions

Patients receive a SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant SC and sargramostim SC on day 0. Treatment repeats every 2 weeks for up to 4 doses in the absence of disease progression or unacceptable toxicity. Patients also receive octreotide acetate IM on day 0. Cycles of octreotide acetate repeat every 28 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients who remain free of tumor progression at 6 months and do not develop any regimen-related toxicity or serious adverse events will be eligible to receive additional doses of the vaccine and sargramostim every 3 months, for up to 1 year from the start of treatment.

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

NeuroEndocrine Tumor Research Foundation (NETRF)

Collaborator

Trials

2

Recruited

60+

Findings from Research

The study identified two survivin peptides that effectively generated specific CD8+ T cell responses in mice, with a focus on the SVN(57-64) peptide, which is identical to a region in human survivin, suggesting its potential as a target for human cancer vaccines.

The SVN(53-67) peptide, which includes multiple epitopes, was shown to produce stronger anti-tumor responses and significantly prolong survival in mice with gliomas, highlighting the advantage of using peptides that can activate both CD8+ cytotoxic T cells and CD4+ helper T cells in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic effect of a T helper cell supported CTL response induced by a survivin peptide vaccine against murine cerebral glioma. Ciesielski, MJ., Kozbor, D., Castanaro, CA., 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]

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 SVX vaccine, which targets the tumor antigen survivin using long synthetic peptides, demonstrated strong immunogenicity and therapeutic efficacy in both healthy individuals and cancer patients, showing the potential to generate robust T-cell responses.

In murine tumor models, the SVX vaccine not only effectively eradicated tumors but also created long-lasting memory T-cell responses and improved the tumor microenvironment by increasing the infiltration of CD4+ and CD8+ T cells, suggesting a promising approach for cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High Therapeutic Efficacy of a New Survivin LSP-Cancer Vaccine Containing CD4+ and CD8+ T-Cell Epitopes. Onodi, F., Maherzi-Mechalikh, C., Mougel, A., et al.[2020]

The study involved 21 patients with high-grade serous ovarian cancer treated with a vaccine and bevacizumab, showing that the treatment was generally well tolerated, with only one case of severe toxicity and a small percentage experiencing significant side effects.

While the vaccine induced an immunogenic response in a majority of patients, this response did not correlate with improved survival outcomes, although increased levels of IL-8 were linked to better progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of patients with recurrent ovarian cancer treated with a polyvalent vaccine with bevacizumab combination. Kahn, RM., Ragupathi, G., Zhou, QC., et al.[2023]

The p53 synthetic long peptide (p53-SLP) vaccine was found to be safe for use in patients with metastatic colorectal cancer, with limited toxicity primarily at the vaccination site.

The vaccine successfully induced p53-specific T-cell responses in 9 out of 10 patients, with some T-cell reactivity persisting for at least 6 months, indicating its potential effectiveness as an immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of p53-specific immunity by a p53 synthetic long peptide vaccine in patients treated for metastatic colorectal cancer. Speetjens, FM., Kuppen, PJ., Welters, MJ., et al.[2021]

The study involved 16 end-stage colorectal cancer patients receiving three vaccinations of a canarypox virus encoding the p53 gene, with no serious toxicity or autoimmune reactions observed, indicating a favorable safety profile for the treatment.

Some patients developed immune responses against p53, and one patient showed stable disease after a second treatment cycle, suggesting potential efficacy in inducing an immune response, although most patients experienced disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of intravenous administration of a canarypox virus encoding the human wild-type p53 gene in colorectal cancer patients. Menon, AG., Kuppen, PJ., van der Burg, SH., et al.[2012]

The study evaluated a survivin-derived CD4(+) T cell epitope in a multipeptide immunotherapy trial for prostate cancer, showing that it can effectively stimulate robust CD4(+) T cell responses in vaccinated patients.

This epitope is presented by multiple HLA-DRB1 molecules and is naturally processed by dendritic cells, indicating its potential for broad immunogenicity and usefulness in enhancing T helper cell responses across various tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Promiscuous survivin peptide induces robust CD4+ T-cell responses in the majority of vaccinated cancer patients. Widenmeyer, M., Griesemann, H., Stevanović, S., et al.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Therapeutic effect of a T helper cell supported CTL response induced by a survivin peptide vaccine against murine cerebral glioma. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

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

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

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

High Therapeutic Efficacy of a New Survivin LSP-Cancer Vaccine Containing CD4+ and CD8+ T-Cell Epitopes. [2020]

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

Long-term outcomes of patients with recurrent ovarian cancer treated with a polyvalent vaccine with bevacizumab combination. [2023]

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

Induction of p53-specific immunity by a p53 synthetic long peptide vaccine in patients treated for metastatic colorectal cancer. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Safety of intravenous administration of a canarypox virus encoding the human wild-type p53 gene in colorectal cancer patients. [2012]

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

Promiscuous survivin peptide induces robust CD4+ T-cell responses in the majority of vaccinated cancer patients. [2021]