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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a new vaccine, made from small protein pieces called peptides, can help the immune system target and kill neuroendocrine tumors, a type of cancer that can spread. The vaccine, known as SVN53-67/M57-KLH Peptide Vaccine, aims to train the immune system to recognize and attack cancer cells. Individuals with neuroendocrine tumors that have grown in the last six months and contain a specific protein, survivin, in their tumor tissue might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that the SVN53-67/M57-KLH Peptide Vaccine is likely to be safe for humans?

Research has shown that the SurVaxM vaccine is generally safe for people. In earlier studies, patients who received this vaccine experienced manageable side effects. These studies aimed to assess the vaccine's safety and tolerability. The results suggest that most patients do not experience serious reactions. However, as this is a Phase 1 trial, the primary goal is to learn about safety and side effects. Prospective participants may find these early results reassuring. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for carcinoid tumors, which often focus on symptom control through medications like octreotide, the SVN53-67/M57-KLH peptide vaccine targets the tumor itself. This vaccine introduces a new mechanism of action by stimulating the body's immune system to recognize and attack carcinoid tumor cells. Researchers are excited about this approach because it has the potential to offer a more targeted and less invasive treatment option, which might lead to improved tumor control and possibly fewer side effects compared to conventional therapies.

What evidence suggests that this peptide vaccine could be effective for neuroendocrine tumors?

Research has shown that the SVN53-67/M57-KLH peptide vaccine, also known as SurVaxM, can help the immune system attack cancer cells. Studies have found that this vaccine targets survivin, a protein present in many cancer cells, including those in neuroendocrine tumors. In lab tests, the vaccine led to strong anti-tumor responses and increased survival in mice with cancer. Early human studies demonstrated that the vaccine can trigger an immune response against cancer cells with survivin. These findings suggest that the vaccine might help the body fight neuroendocrine tumors by boosting the immune system. Participants in this trial will receive the SVN53-67/M57-KLH peptide vaccine along with octreotide, which is part of the treatment regimen being tested. ^{2 3 6 7 8}

Who Is on the Research Team?

Renuka V. Iyer

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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]

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 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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03879694

NCT03879694 | Survivin Long Peptide Vaccine in Treating ... 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03879694?cond=Carcinoid%20Tumor&term=Iyer,%20Renuka&rank=2

Survivin Long Peptide Vaccine in Treating Patients With ... 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 ...

3. cancer.gov cancer.gov/clinicaltrials/NCI-2023-09345

Temozolomide and Survivin Long Peptide Vaccine ... SVN53-67/M57-KLH peptide vaccine (SurVaxM) is a vaccine that has been shown to produce an immune system response against cancer cells that express a survivin ...

4. withpower.com withpower.com/trial/phase-1-neoplasms-5-2019-6d4c0?lat=34.60184&lng=-117.81218

Peptide Vaccine for Carcinoid Tumor The SVN(53-67) peptide, which includes multiple epitopes, was shown to produce stronger anti-tumor responses and significantly prolong survival in mice with ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27576783/

Clinical study of a survivin long peptide vaccine (SurVaxM) in ... The conjugated survivin peptide mimic SurVaxM (SVN53-67/M57-KLH) could stimulate an anti-tumor immune response against murine glioma in vivo, as well as human ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03879694

NCT03879694 | Survivin Long Peptide Vaccine in Treating ... To assess safety, tolerability and toxicity of SVN53-67/M57-KLH peptide vaccine (SurVaxM) in emulsion with incomplete Freund's adjuvant (montanide ISA 51) and ...

7. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/svn53-67-m57-klh-peptide-vaccine?pn=1

Clinical Trials Using SVN53-67/M57-KLH Peptide Vaccine NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying svn53-67/m57-klh peptide vaccine.

8. delta.larvol.com delta.larvol.com/Products/?ProductId=6620be65-020e-4867-b807-6fbb5cbf9020

SurVaxM (SVN53-67/M57-KLH peptide vaccine) / MimiVax, ... Biomarker Analysis Reveals Clues to Long-Term Survival in Glioblastoma Patients Treated with SurVaxM (Newswise) - "Investigators used whole-exome and RNA ...