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

Trial Summary

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.

What data supports the effectiveness of the Folate Receptor Alpha Vaccine for Ovarian Cancer treatment?

Research shows that a similar vaccine using dendritic cells (special immune cells) loaded with folate receptor alpha can safely boost the immune system and help keep ovarian cancer from coming back in some patients. In a study, 39% of patients remained cancer-free for a median of over four years after receiving the vaccine. ^{1 2 3 4 5}

Is the Folate Receptor Alpha Vaccine for Ovarian Cancer safe for humans?

The Folate Receptor Alpha Vaccine has been tested in clinical trials and is generally safe, with no severe side effects reported. Most side effects were mild, such as injection site reactions and fatigue. ^{1 2 3 6 7}

How is the Folate Receptor Alpha Vaccine treatment different from other ovarian cancer treatments?

The Folate Receptor Alpha Vaccine for ovarian cancer is unique because it uses a patient's own dendritic cells (a type of immune cell) loaded with specific proteins from the cancer to stimulate the immune system, aiming to prolong remission by inducing targeted immune responses, unlike traditional treatments that may not specifically target the immune system in this way. ^{1 3 7 8 9}

What is the purpose of this trial?

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, fallopian tube or primary peritoneal cancer. FRαDCs, a dendritic cell vaccine, is made from a person's white blood cells. The white blood cells are treated in the laboratory to make dendritic cells (a type of immune cell) mixed with folate receptor alpha (FRalpha), a protein found in high levels on ovarian tumor cells. FRαDCs work by boosting the immune system to recognize and destroy the tumor cells by targeting the FRalpha protein on the tumor cell. Placebo is an inactive substance that looks the same as, and is given the same way as, the active drug or treatment being tested. The effects of the active drug are compared to the effects of the placebo. Giving FRαDCs may work better in preventing or delaying recurrence compared to placebo in patients with stage III or IV ovarian, fallopian tube, or primary peritoneal cancer.

Research Team

Matthew S. Block, MD, PhD

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Th17-inducing autologous dendritic cell vaccination promotes antigen-specific cellular and humoral immunity in ovarian cancer patients. [2020]

2. United Arab Emirates pubmed.ncbi.nlm.nih.gov

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

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

A multipeptide vaccine is safe and elicits T-cell responses in participants with advanced stage ovarian cancer. [2020]

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

The role of dendritic cells in cytotoxic immune response regulation in ovarian cancer micro-environment. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Advanced clinical trials of dendritic cell vaccines in ovarian cancer. [2021]

6. United States 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. [2017]

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

Folate Receptor Alpha Peptide Vaccine Generates Immunity in Breast and Ovarian Cancer Patients. [2023]

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

Vaccine implications of folate binding protein, a novel cytotoxic T lymphocyte-recognized antigen system in epithelial cancers. [2020]

9. United States 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. [2021]