Folate Receptor Alpha Vaccine for Ovarian Cancer

Recruiting at 2 trial locations

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Immunosuppressants, PARP inhibitors

Disqualifiers: BRCA mutations, Active malignancy, others

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

Compensation: Varies

Number of Visits: 15

Duration: 12 cycles (up to 8 years)

78 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new vaccine made from a person's white blood cells to combat advanced ovarian, fallopian tube, or primary peritoneal cancer. The vaccine, called the Multi-epitope Folate Receptor Alpha-loaded Dendritic Cell Vaccine, aims to train the immune system to recognize and attack cancer cells by targeting a specific protein on them. Participants will receive either the actual vaccine or a placebo (a harmless, inactive treatment) to determine if the vaccine can more effectively prevent cancer recurrence. Those with stage III or IV ovarian, fallopian tube, or primary peritoneal cancer, who have completed surgery and chemotherapy, and do not have BRCA1/BRCA2 mutations may be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant advancements in cancer therapy.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on certain treatments like chemotherapy, radiation, or immunotherapy within 4 weeks before joining, and you should not be on systemic immunosuppressive medication within 2 weeks prior to registration.

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

Research has shown that the folate receptor alpha dendritic cell vaccine (FRαDCs) is generally well-tolerated. In earlier studies, patients experienced some side effects, mostly mild. These included common reactions like redness or swelling at the injection site, similar to reactions from a regular vaccine.

Some participants also reported mild flu-like symptoms, such as fever or tiredness. These side effects were temporary and resolved on their own. The vaccine is designed to help the immune system better target cancer cells. While no treatment is without risk, the safety data so far suggests that FRαDCs have a manageable safety profile for those considering participation in a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ovarian cancer?

Researchers are excited about the Folate Receptor Alpha Vaccine for ovarian cancer because it offers a novel approach compared to the standard chemotherapy and targeted therapies like PARP inhibitors. This treatment involves a dendritic cell vaccine loaded with multi-epitopes of the folate receptor alpha, which aims to harness the body's immune system to specifically target and attack cancer cells. Unlike traditional treatments that can affect both cancerous and healthy cells, this vaccine is designed to provide a more targeted immune response, potentially reducing side effects and improving efficacy. By focusing on the folate receptor, which is often overexpressed in ovarian cancer cells, this vaccine promises a more precise and personalized treatment option.

What evidence suggests that the Folate Receptor Alpha Vaccine could be an effective treatment for ovarian cancer?

Research has shown that the folate receptor alpha-loaded dendritic cell vaccine (FRαDCs), which participants in this trial may receive, might help treat certain cancers. This vaccine aids the immune system in identifying and attacking cancer cells by targeting a protein called FRalpha, often found on ovarian cancer cells. Studies have demonstrated that similar vaccines can strengthen the immune system in ovarian cancer patients and may enhance outcomes after standard treatments. Early findings also suggest that these vaccines can generate a strong immune response against cancer cells. Although more research is needed, these early results are promising for patients with advanced ovarian cancer. ^{1 3 5 6 7}

Who Is on the Research Team?

Matthew S. Block, MD, PhD

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for patients with advanced ovarian, fallopian tube, or primary peritoneal cancer (stage III or IV). Specific eligibility criteria are not provided but typically include factors like age, overall health status, and the extent of disease progression.

Inclusion Criteria

Platelet count ≥ 75,000/mm^3 (≤ 15 days prior to registration)

Expected survival ≥ 6 months

Monocytes ≥ 0.25 x 10^9/L (≤ 15 days prior to registration)

Exclusion Criteria

I have had radiation therapy for my cancer.

I am immunocompromised or HIV positive and on antiretroviral therapy.

I haven't had certain cancer treatments in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive FRalphaDCs or placebo intradermally on day 1 of each cycle. Cycles repeat every 21 days for cycles 1-5 and every 91 days for cycles 6-12.

12 cycles (up to 8 years)

12 visits (in-person)

Follow-up

Participants are monitored for recurrence-free survival and overall survival every 3 months for up to month 36, then every 3 months until progression, followed by every 6 months for up to year 8.

Up to 8 years

Regular visits every 3-6 months

What Are the Treatments Tested in This Trial?

Interventions

• Multi-epitope Folate Receptor Alpha-loaded Dendritic Cell Vaccine
• Placebo Administration

Trial Overview The trial is testing a new vaccine made from the patient's own white blood cells called FRαDCs against a placebo. The vaccine aims to boost the immune system to target and destroy tumor cells by recognizing a protein on them.

How Is the Trial Designed?

Group I: Arm I (FRalphaDCs) Experimental Treatment 8 Interventions

Patients may receive Td or Tdap IM prior to undergoing leukapheresis. Patients receive FRalphaDCs ID on day 1 of each cycle. Cycles repeat every 21 days for cycles 1-5 and then repeat every 91 days for cycles 6-12 in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo biopsy prior to apheresis and optionally at end of treatment, and blood sample collection, CT and/or MRI throughout the study.

Group II: Arm II (placebo) Placebo Group 8 Interventions

Patients may receive Td or Tdap IM prior to undergoing leukapheresis. Patients receive placebo ID on day 1 of each cycle. Cycles repeat every 21 days for cycles 1-5 and then repeat every 91 days for cycles 6-12 in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo biopsy prior to apheresis and optionally at end of treatment, and blood sample collection, CT and/or MRI throughout the study.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

The heptavalent antigen-KLH plus QS21 vaccine was well tolerated in a pilot trial with 11 patients, showing only mild side effects like fatigue and localized reactions, with no significant safety concerns or evidence of autoimmunity.

The vaccine successfully induced antibody responses against five out of seven targeted cancer antigens, with most patients developing responses to at least three antigens, suggesting potential for further investigation in larger efficacy trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of a heptavalent vaccine-keyhole limpet hemocyanin conjugate plus QS21 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer. Sabbatini, PJ., Ragupathi, G., Hood, C., et al.[2017]

Dendritic cell (DC) therapy shows promise as a novel treatment for ovarian cancer by potentially inducing effective anti-tumor immunity, which is crucial since relapsed ovarian cancer remains incurable.

The major challenge in developing DC-based vaccines for ovarian cancer is the lack of clearly defined tumor-specific antigens that T cells can recognize, highlighting the need for further research in identifying suitable candidates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of dendritic cells in cytotoxic immune response regulation in ovarian cancer micro-environment. Wertel, I., Barczynski, B., Kotarski, J.[2019]

In a phase 1 study involving 9 participants with ovarian cancer, a peptide-based vaccine was found to be safe, with all reported side effects being mild (grade 1 to 2), including injection site reactions and fatigue.

The vaccine elicited T-cell responses in 89% of participants after stimulation, indicating immunogenicity, but the responses were of low potency, suggesting that future studies may need to combine this vaccine with additional immunomodulatory treatments to enhance T-cell activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multipeptide vaccine is safe and elicits T-cell responses in participants with advanced stage ovarian cancer. Chianese-Bullock, KA., Irvin, WP., Petroni, GR., et al.[2020]

The study identifies the human high-affinity folate binding protein (FBP) as a promising target for cancer immunotherapy, showing that its antigenic peptides can stimulate immune responses in both ovarian and breast cancers.

FBP peptides enhance the cytotoxic activity of tumor-associated lymphocytes against various epithelial tumors, indicating their potential for developing a broadly applicable vaccine for multiple types of epithelial-derived cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine implications of folate binding protein, a novel cytotoxic T lymphocyte-recognized antigen system in epithelial cancers. Peoples, GE., Anderson, BW., Lee, TV., et al.[2020]

The study developed a method to create synthetic oligopeptides from unique ovarian cancer biomarkers, which could lead to highly specific immune responses against ovarian cancer.

These oligopeptides are designed to be non-crossreactive, potentially enhancing their effectiveness for immunodiagnostics, immunoprevention, and immunotherapy in ovarian cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oligopeptides for Immunotherapy Approaches in Ovarian Cancer Treatment. Kanduc, D.[2020]

The phase I clinical trial demonstrated that a vaccine targeting the folate receptor alpha (FR) is safe and well-tolerated in patients with ovarian or breast cancer, with over 90% of participants showing an immune response after vaccination.

Immunity to the FR developed slowly, reaching its peak around 5 months after vaccination, but persisted for at least 12 months, indicating the potential for long-lasting immune protection against tumors expressing FR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Folate Receptor Alpha Peptide Vaccine Generates Immunity in Breast and Ovarian Cancer Patients. Kalli, KR., Block, MS., Kasi, PM., et al.[2023]

The phase I clinical trial involving 19 ovarian cancer patients demonstrated that a vaccine using Th17-inducing dendritic cells is safe, with no severe adverse events reported, and successfully induces immune responses against the folate receptor alpha (FRα).

Of the 18 patients evaluated for efficacy, 39% remained recurrence-free after a median follow-up of 49.2 months, suggesting that the vaccine may contribute to prolonged remission in ovarian cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Th17-inducing autologous dendritic cell vaccination promotes antigen-specific cellular and humoral immunity in ovarian cancer patients. Block, MS., Dietz, AB., Gustafson, MP., et al.[2020]

The E39 + GM-CSF vaccine was found to be safe and well-tolerated in a phase I/IIa trial involving 51 patients, with no significant clinicopathologic differences between the vaccine group and the control group.

At the 24-month mark, disease-free survival (DFS) was significantly improved in patients receiving the optimal dose of 1000 μg of E39, particularly in those with low folate-binding protein (FBP) expression, suggesting the vaccine may effectively prevent recurrences in high-risk ovarian and endometrial cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final analysis of a phase I/IIa trial of the folate-binding protein-derived E39 peptide vaccine to prevent recurrence in ovarian and endometrial cancer patients. Brown, TA., Byrd, K., Vreeland, TJ., et al.[2021]

Dendritic cell (DC) vaccines have shown promising clinical benefits and safety in phase II trials for treating epithelial ovarian cancer (EOC), which is a leading cause of gynecologic cancer deaths.

Currently, DC vaccines are being evaluated in a phase III clinical trial, indicating a significant step towards potentially improving treatment options for EOC patients who have limited chemotherapy choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced clinical trials of dendritic cell vaccines in ovarian cancer. Guo, Q., Yang, Q., Li, J., et al.[2021]

Citations

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NCT06639074 | Folate Receptor Alpha Dendritic Cells ... This phase II trial compares the effect of folate receptor alpha dendritic cells (FRαDCs) to placebo in treating patients with stage III or IV ovarian, ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39068739/

Vaccination with folate receptor-alpha peptides in patients ... We tested the hypothesis that FRα peptide immunization could improve outcomes in patients with EOC following response to platinum-based therapy.

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NCT05920798 | Vaccine Therapy Plus Pembrolizumab in ... This phase I/II trial tests the safety, side effects, best dose, and effectiveness of multi-epitope folate receptor alpha-loaded dendritic cell vaccine ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7560895/

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6. clinicaltrials.gov clinicaltrials.gov/study/NCT06639074

NCT06639074 | Folate Receptor Alpha Dendritic Cells ... This phase II trial compares the effect of folate receptor alpha dendritic cells (FRαDCs) to placebo in treating patients with stage III or IV ovarian, ...

7. clinicaltrial.be clinicaltrial.be/en/details/11906?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Vaccine Therapy for Patients With Stage IIIC-IV Ovarian E... I. Determine the safety and tolerability of folate receptor alpha dendritic cell (FRalphaDC) vaccination (folate receptor alpha-peptide loaded ...