Trial Title:
Folate Receptor Alpha Dendritic Cells (FRαDCs) or Placebo for the Treatment of Patients With Stage III or IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer, FAROUT Trial
NCT ID:
NCT06639074
Condition:
Advanced Fallopian Tube Carcinoma
Advanced Fallopian Tube High Grade Serous Adenocarcinoma
Advanced Ovarian Carcinoma
Advanced Ovarian Carcinosarcoma
Advanced Ovarian Clear Cell Adenocarcinoma
Advanced Ovarian Endometrioid Adenocarcinoma
Advanced Ovarian High Grade Serous Adenocarcinoma
Advanced Primary Peritoneal Carcinoma
Advanced Primary Peritoneal High Grade Serous Adenocarcinoma
Fallopian Tube Carcinosarcoma
Fallopian Tube Clear Cell Adenocarcinoma
Fallopian Tube Endometrioid Adenocarcinoma
FIGO Stage III Ovarian Cancer 2014
FIGO Stage IV Ovarian Cancer 2014
Ovarian Mixed Cell Adenocarcinoma
Primary Peritoneal Carcinosarcoma
Primary Peritoneal Clear Cell Adenocarcinoma
Primary Peritoneal Endometrioid Adenocarcinoma
Conditions: Official terms:
Carcinoma
Adenocarcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Cystadenocarcinoma, Serous
Carcinoma, Endometrioid
Carcinosarcoma
Mixed Tumor, Mullerian
Adenocarcinoma, Clear Cell
Vaccines
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Triple (Participant, Care Provider, Investigator)
Masking description:
Patient, provider and principal investigator are blinded
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Arm I (FRalphaDCs)
Arm group label:
Arm II (placebo)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Arm I (FRalphaDCs)
Arm group label:
Arm II (placebo)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Arm I (FRalphaDCs)
Arm group label:
Arm II (placebo)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Biological
Intervention name:
Diphtheria Toxoid/Tetanus Toxoid/Acellular Pertussis Vaccine Adsorbed
Description:
Given IM
Arm group label:
Arm I (FRalphaDCs)
Arm group label:
Arm II (placebo)
Other name:
Adacel
Other name:
Daptacel
Other name:
Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed
Other name:
Diphtheria Toxoid Tetanus Toxoid Acellular Pertussis Vaccine Adsorbed
Other name:
Diphtheria Toxoid/Tetanus Toxoid/Acellular Pertussis Vaccine
Other name:
DTaP
Other name:
Infanrix
Other name:
Tripedia
Intervention type:
Procedure
Intervention name:
Leukapheresis
Description:
Undergo leukapheresis
Arm group label:
Arm I (FRalphaDCs)
Arm group label:
Arm II (placebo)
Other name:
Leukocyte Adsorptive Apheresis
Other name:
Leukocytopheresis
Other name:
Therapeutic Leukopheresis
Other name:
White Blood Cell Reduction Apheresis
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Arm I (FRalphaDCs)
Arm group label:
Arm II (placebo)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Biological
Intervention name:
Multi-epitope Folate Receptor Alpha-loaded Dendritic Cell Vaccine
Description:
Given ID
Arm group label:
Arm I (FRalphaDCs)
Other name:
FRaDC Vaccine
Other name:
FRalphaDC Vaccine
Intervention type:
Drug
Intervention name:
Placebo Administration
Description:
Given ID
Arm group label:
Arm II (placebo)
Intervention type:
Biological
Intervention name:
Tetanus and Diphtheria Toxoids Adsorbed
Description:
Given IM
Arm group label:
Arm I (FRalphaDCs)
Arm group label:
Arm II (placebo)
Other name:
DECAVAC
Other name:
Td
Other name:
Tetanus and Diphtheria Toxoids Adsorbed for Adult Use
Summary:
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.
Detailed description:
PRIMARY OBJECTIVE:
I. Compare recurrence-free survival (RFS) in advanced ovarian carcinoma (OC) patients
vaccinated with multi-epitope folate receptor alpha-loaded dendritic cell vaccine
(FRαDCs) (active vaccine) versus placebo.
SECONDARY OBJECTIVES:
I. Compare overall survival (OS) in advanced OC patients vaccinated with FRαDCs versus
placebo.
II. Compare the adverse event (AE) profile of FRαDCs with that of placebo.
CORRELATIVE RESEARCH OBJECTIVES:
I. Assess association of pre-existing immune microenvironment with RFS. II. Characterize
the T cell and antibody responses to FRα and assess the association between the emergence
of immunity and RFS.
III. Assess for epitope spreading and evaluate the association between epitope spreading
and RFS.
IV. Compare archival tissue from surgery with post-recurrence biopsy tissue in those
patients who develop recurrence to assess for common immune evasion mechanisms.
V. Evaluate differences in ribonucleic acid (RNA) expression of FRαDCs and its
association with RFS.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients may receive tetanus and diphtheria vaccine (Td) or
tetanus-diphtheria-accellular pertussis vaccine (Tdap) intramuscularly (IM) prior to
undergoing leukapheresis. Patients receive FRalphaDCs intradermally (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, computed tomography (CT) and/or magnetic resonance imaging (MRI)
throughout the study.
ARM II: 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.
After completion of study treatment, patients are followed up every 3 months for up to
month 36 then every 3 months until progression followed by every 6 months for up to year
8.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age ≥ 18 years
- Histological confirmation of Federation of Gynecology and Obstetrics (FIGO) stage
III or stage IV epithelial ovarian, fallopian tube, or primary peritoneal cancer.
NOTE: Histologic confirmation of the primary tumor is required. Eligible histotypes
include high grade serous; endometrioid; and clear cell carcinoma, as these
histotypes have high expression of FRα (Kalli, Oberg, Keeney, & et al., 2008). Mixed
carcinomas, including carcinosarcomas, with ≥ 50% of the tumor comprised of high
grade serous; and/or endometrioid; and/or clear cell carcinoma are eligible
- Completion of cytoreductive surgery and one (and only one) course of platinum-based
chemotherapy (5-9 cycles) ≥ 4 but ≤ 12 weeks prior to registration
- NOTE: Cytoreductive surgery may have been prior to or after one or more cycles
of chemotherapy and must include hysterectomy and bilateral
salpingo-oophorectomy (if the uterus and/or ovaries were not previously
removed)
- NOTE: Patients may have had more than one chemotherapy regimen (examples:
paclitaxel/carboplatin switched to docetaxel/carboplatin due to allergy; or
weekly treatment switched to every 3-weekly treatment due to intolerance), but
may not have received a separate course of treatment for recurrent OC
- NOTE: Patients may receive both neoadjuvant and adjuvant chemotherapy provided
both regimens are platinum-based and total nine (9) or fewer chemotherapy
cycles
- Germline and somatic genetic testing have been completed
- NOTE: No pathogenic mutations of BRCA1/BRCA2 are allowed
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
- Expected survival ≥ 6 months
- Hemoglobin ≥ 8.5 g/dL (≤ 15 days prior to registration)
- Absolute neutrophil count (ANC) ≥ 1000/mm^3 (≤ 15 days prior to registration)
- Platelet count ≥ 75,000/mm^3 (≤ 15 days prior to registration)
- Lymphocytes ≥ 0.3 x 10^9/L (≤ 15 days prior to registration)
- Monocytes ≥ 0.25 x 10^9/L (≤ 15 days prior to registration)
- Total bilirubin ≤ upper limit of normal (ULN), unless patient has a documented
history of Gilbert's disease, then direct bilirubin ≤ ULN (≤ 15 days prior to
registration)
- Aspartate transaminase (AST) ≤ 3 x ULN (≤ 15 days prior to registration)
- Creatinine clearance ≥ 30 mL/min per Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) creatinine equation (≤ 15 days prior to registration)
- Provide written informed consent
- Willing to provide mandatory blood specimens for correlative research
- Willing to provide archival tissue specimen for correlative research
- Willing to return a participating institution for follow-up (during the active
monitoring phase of the study)
- Willing to undergo a tetanus vaccination (if not performed ≤ 365 days prior to
registration)
- Willing to have a central access line placed, if needed (as determined during venous
access assessment)
Exclusion Criteria:
- 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
- Evidence of disease at the time of registration, including clinical concern for
disease recurrence based on each of the following:
- Evidence of disease by history and physical exam
- CA125 outside institutional normal limits
- CT (and or MRI) of the chest/abdomen/pelvis demonstrating radiological evidence
of disease performed after completion of chemotherapy ≤ 28 days be-fore
entering study
- Germline or somatic BRCA1 or BRCA2 mutation, as determined by Clinical Laboratory
Improvement Act (CLIA)-approved tests
- Prior radiation therapy for this cancer
- Treatment with chemotherapy, angiogenesis inhibitor therapy, poly (ADP-ribose)
polymerase (PARP) inhibitor therapy, radiation therapy, or other immunotherapy ≤ 4
weeks prior to registration
- Receiving any other standard therapy (angiogenesis inhibitor, PARP inhibitor) or
investigational agent, which would be considered as a treatment for the primary
neoplasm. These agents have been shown to be active in later line therapy and can be
used at that time for patients who relapse after treatment on this trial
- 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
- Immunocompromised patients and patients known to be HIV positive and currently
receiving antiretroviral therapy
- NOTE: Patients known to be HIV positive, but without clinical evidence of an
immunocompromised state, are eligible for this trial
- Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness/social situations that would limit compliance with study
requirements
- EXCEPTIONS: HIV-infected patients on effective anti-retroviral therapy with
undetectable viral load within 6 months are eligible for this trial. For
patients with evidence of hepatitis B virus (HBV) infection, the HBV viral load
must be undetectable on suppressive therapy, if indicated. Patients with a
history of hepatitis C virus (HCV) must have been treated and cured. For
patients with HCV infection who are currently on treatment, they are eligible
if they have an undetectable HCV viral load
- Other active malignancy ≤ 3 years prior to registration
- EXCEPTIONS: Patients with non-melanotic skin cancer, papillary thyroid cancer
not requiring therapy or carcinoma-in-situ are eligible for this trial.
Patients with a prior or concurrent malignancy whose natural history or
treatment does not have the potential to interfere with the safety or efficacy
assessment of the investigational regimen are eligible for this trial. (Contact
site principal investigator [PI] if questions.)
- History of myocardial infarction ≤ 6 months prior to registration, or congestive
heart failure requiring use of ongoing maintenance therapy for life-threatening
ventricular arrhythmias
- NOTE: Patients with known history or current symptoms of cardiac disease, or
history of treatment with cardiotoxic agents, should have a clinical risk
assessment of cardiac function using the New York Heart Association Functional
Classification. To be eligible for this trial, patients should be class 2B or
better
- Treatment with systemic immunosuppressive medication (including, but not limited to,
prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti-tumor necrosis factor [TNF]-alpha agents) ≤ 2 weeks prior to registration, or
anticipation of need for systemic immunosuppressive medication during the course of
the study
- NOTE: Patients who have received acute, low-dose systemic steroids (≤ 10 mg/day
oral prednisone or equivalent) prior to registration or a one-time pulse dose
of systemic immunosuppressant medication (e.g., ≤ 48 hours of corticosteroids
for a contrast allergy) are eligible for the study
- NOTE: The use of inhaled corticosteroids for chronic obstructive pulmonary
disease or asthma, mineralocorticoids (e.g., fludrocortisone), or low-dose
corticosteroids for patients with orthostatic hypotension or adrenocortical
insufficiency is allowed
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Arizona
Address:
City:
Scottsdale
Zip:
85259
Country:
United States
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Nina J. Karlin, MD
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic in Florida
Address:
City:
Jacksonville
Zip:
32224-9980
Country:
United States
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Gerardo Colon-Otero, MD
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Matthew S. Block, MD, PhD
Email:
Principal Investigator
Start date:
November 12, 2024
Completion date:
December 31, 2027
Lead sponsor:
Agency:
Mayo Clinic
Agency class:
Other
Source:
Mayo Clinic
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06639074
https://www.mayo.edu/research/clinical-trials
