Vaccine Therapy Plus Pembrolizumab in Treating Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cavity Cancer
FRAPPE
MC220601, Folate Receptor Alpha Dendritic Cells (FRαDCs) Plus Pembrolizumab for Patients With Advanced Stage Ovarian Cancer (FRAPPE)
4 other identifiers
interventional
40
1 country
3
Brief Summary
This phase I/II trial tests the safety, side effects, best dose, and effectiveness of multi-epitope folate receptor alpha-loaded dendritic cell vaccine (FRalphaDC) with pembrolizumab in treating patients with ovarian, fallopian tube, or primary peritoneal cancer (collectively known as ovarian cancer) that that has come back (after a period of improvement) (recurrent). Ovarian cancer is the most lethal gynecologic malignancy in the United States. While the majority of patients achieve a remission from ovarian cancer with the combination of aggressive cytoreductive surgery and cytotoxic chemotherapy, over 80% of patients develop recurrence within 3 years of completion of treatment. Additional treatments are needed for recurrence, but the standard treatment modalities are non-curative in nature due to the development of drug resistance. As such, there is a great unmet need for treatment strategies that utilize new mechanisms to which drug resistance does not develop. FRalphaDC is a dendritic cell vaccine that is made from the white blood cells collected from a procedure call apheresis. The white blood cells are treated to make dendritic cells, which will then be incubated with peptides, which are pieces of a protein known as "folate receptor alpha" (FRalpha), a protein that is found in high levels on ovarian cancer cells. Dendritic cell vaccines work by boosting the immune system (a system in the body that protect against infection) to recognize and destroy the tumor cells by targeting the FRalpha protein. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving FRalphaDC vaccine with pembrolizumab may be a safe and effective treatment for recurrent ovarian cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Sep 2023
Typical duration for phase_1
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 9, 2023
CompletedFirst Posted
Study publicly available on registry
June 27, 2023
CompletedStudy Start
First participant enrolled
September 28, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 15, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 15, 2027
June 22, 2025
June 1, 2025
3.8 years
June 9, 2023
June 18, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Determine whether the combination of FRαDCs and pembrolizumab has an acceptable toxicity profile.
Three patients will be enrolled to starting dose (dose level 1) and enrollment will pause until each of the first 3 patients have completed cycle 1 of therapy. If zero or one of first 3 patients develops a dose limiting toxicity (DLT) during cycle 1, 3 more patients will be enrolled to dose level 1. If observe at most 1 DLT in the first 6 patients at dose level 1, it will be considered safe and will continue in phase II of trial. If 2 or more of the first 6 patients develop a DLT during cycle 1 for dose level 1, then enrollment will stop and dose level will be decreased. Additional patients will be enrolled in cohorts of 3 to that decreased dose level. If zero or one DLT in the first 6 patients at dose level -1, it will be considered safe and will continue in phase II of trial. Otherwise, if observe 2 or more DLTs in the first 6 patients of dose level -1, enrollment will stop until the Study Team adjusts the treatment plan with input from the Data Safety Monitoring Board.
Up to 21 days
Confirm objective response rate (ORR)
Defined as the proportion of patients with a complete response (CR) or partial response (PR). If at least 7 confirmed responses are observed in the first 32 eligible patients (22%), the combination treatment will be considered worthy of further investigation.
Up to 5 years
Secondary Outcomes (5)
Disease control rate
Up to 5 years
Duration of response
Up to 5 years
Progression free survival (PFS)
Up to 5 years
Overall survival (OS)
Up to 5 years
Incidence of adverse events
Up to 5 years
Study Arms (1)
Treatment (apheresis, FRalphaDC, pembrolizumab)
EXPERIMENTALPatients undergo apheresis for multi-epitope folate receptor alpha-loaded dendritic cell vaccine manufacturing on study. Patients then receive multi-epitope folate receptor alpha-loaded dendritic cell vaccine ID on day 1 of cycles 1-5 and pembrolizumab IV over 30 minutes on day 1 of cycles 1-8. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patient then receive multi-epitope folate receptor alpha-loaded dendritic cell vaccine ID on day 1 of odd cycles and pembrolizumab IV over 30 minutes on day 1 of remaining cycles. Cycles repeat every 42 days for up to cycle 22 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI as well as blood sample collection throughout the trial. Patients undergo biopsy on study.
Interventions
Undergo biopsy
Undergo blood sample collection
Undergo CT
Undergo MRI
Given ID
Given IV
Undergo apheresis
Eligibility Criteria
You may qualify if:
- Age \>= 18 years
- Histologically confirmed recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer NOTE: Histologic confirmation of the primary tumor or recurrent tumor per pathology report is required. Eligible histotypes include high grade serous; endometrioid; and clear cell carcinoma, as these histotypes have high expression of FRalpha. Mixed carcinomas, including carcinosarcomas, with \>= 50% of the tumor comprised of high grade serous; and/or endometrioid; and/or clear cell carcinoma are eligible
- Ovarian cancer (OC) recurrence - Platinum sensitivity/resistance
- Platinum-refractory (defined as recurrence or progression of OC =\< 30 days of the last dose of platinum-based chemotherapy)
- Platinum-resistant (defined as recurrence or progression of OC between 31-180 days of the last dose of platinum-based chemotherapy)
- Platinum-sensitive (defined as recurrence or progression \>=181 days after the last dose of platinum-based chemotherapy).
- NOTE: Any number of prior therapies or maintenance regimens for OC are allowed
- At least one of the following:
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria AND/OR
- CA-125-evaluable disease, as defined by the Gynecologic Cancer InterGroup (GCIG)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Hemoglobin \>= 8.5 g/dL (obtained =\< 15 days prior to registration)
- Absolute neutrophil count (ANC) \>= 1000/mm\^3 (obtained =\< 15 days prior to registration)
- Platelet count \>= 75,000/mm\^3 (obtained =\< 15 days prior to registration)
- Lymphocytes \>= 0.3 x 10\^9/L (obtained =\< 15 days prior to registration)
- +11 more criteria
You may not qualify if:
- Any of the following because this study involves an investigational agent, the genotoxic, mutagenic and teratogenic effects of which on the developing fetus and newborn are unknown
- Pregnant persons
- Nursing persons
- Persons of childbearing potential or able to father a child who are unwilling to employ adequate contraception
- Prior treatment for ovarian cancer with an anti-PD-1 or anti-PD-L1 monoclonal antibody
- Treatment with IV anti-cancer therapy =\< 3 weeks prior to registration or with oral anti-cancer therapy =\< 1 week prior to registration NOTE: Since treatment will begin no sooner than 4 weeks after registration due to the need for apheresis and manufacturing of the FRαDC product, a "wash-out" period prior to registration will cause a gap of at least 5 weeks between the last anti-cancer treatment and initiation of protocol therapy
- Grade 2 or higher symptoms attributed to OC OR disease measuring \> 5 cm in long axis (non-nodal lesions), or \> 5 cm in short axis (nodal lesions) OR disease that, in the judgement of the treating investigator, is likely to become symptomatic in the next 8 weeks (ex. moderate ascites)
- NOTE: Since patients will not receive therapy for cancer until 3-4 weeks after apheresis--which is potentially 6-8 weeks after registration --patients with symptomatic OC or an elevated tumor burden may experience significant progression prior starting therapy and should not be treated on this protocol).
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- Uncontrolled human immunodeficiency virus (HIV) infection and/or HIV-infected patients with a history of Kaposi's sarcoma and/or multicentric Castleman disease.
- NOTE: HIV-infected participants must have well-controlled HIV on anti-retroviral therapy (ART), defined as:
- Participants on ART must have a CD4+ T-cell count ≥ 350 cells/mm\^3 at the time of screening
- Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV ribonucleic acid (RNA) level below 50 or the lower limit of quantification derivation technique (LLOQ) (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening
- It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months
- Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (day 1) and agree to continue ART throughout the study
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mayo Cliniclead
- NanoPass Technologies Ltdcollaborator
- National Cancer Institute (NCI)collaborator
Study Sites (3)
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Matthew S. Block, MD, PhD
Mayo Clinic in Rochester
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 9, 2023
First Posted
June 27, 2023
Study Start
September 28, 2023
Primary Completion (Estimated)
July 15, 2027
Study Completion (Estimated)
July 15, 2027
Last Updated
June 22, 2025
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will not share