Trial Title:
A Study of FRaDCs for Ovarian Cancer
NCT ID:
NCT05920798
Condition:
Fallopian Tube Carcinosarcoma
Primary Peritoneal Carcinosarcoma
Recurrent Fallopian Tube Carcinoma
Recurrent Fallopian Tube Clear Cell Adenocarcinoma
Recurrent Fallopian Tube Endometrioid Adenocarcinoma
Recurrent Fallopian Tube High Grade Serous Adenocarcinoma
Recurrent Ovarian Carcinoma
Recurrent Ovarian Carcinosarcoma
Recurrent Ovarian Clear Cell Adenocarcinoma
Recurrent Ovarian Endometrioid Adenocarcinoma
Recurrent Ovarian High Grade Serous Adenocarcinoma
Recurrent Primary Peritoneal Carcinoma
Recurrent Primary Peritoneal Clear Cell Adenocarcinoma
Recurrent Primary Peritoneal Endometrioid Adenocarcinoma
Recurrent Primary Peritoneal High Grade Serous Adenocarcinoma
Conditions: Official terms:
Carcinoma
Adenocarcinoma
Cystadenocarcinoma, Serous
Carcinoma, Endometrioid
Carcinosarcoma
Mixed Tumor, Mullerian
Adenocarcinoma, Clear Cell
Recurrence
Pembrolizumab
Vaccines
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Treatment (apheresis, FRalphaDC, pembrolizumab)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (apheresis, FRalphaDC, pembrolizumab)
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:
Treatment (apheresis, FRalphaDC, pembrolizumab)
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:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (apheresis, FRalphaDC, pembrolizumab)
Other name:
Magnetic Resonance
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:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Intervention type:
Biological
Intervention name:
Multi-epitope Folate Receptor Alpha-loaded Dendritic Cell Vaccine
Description:
Given ID
Arm group label:
Treatment (apheresis, FRalphaDC, pembrolizumab)
Other name:
FRaDC Vaccine
Other name:
FRalphaDC Vaccine
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Given IV
Arm group label:
Treatment (apheresis, FRalphaDC, pembrolizumab)
Other name:
Keytruda
Other name:
Lambrolizumab
Other name:
MK-3475
Other name:
SCH 900475
Intervention type:
Procedure
Intervention name:
Pheresis
Description:
Undergo apheresis
Arm group label:
Treatment (apheresis, FRalphaDC, pembrolizumab)
Other name:
Apheresed
Other name:
Apheresis
Other name:
Blood Component Removal
Other name:
Collection, Apheresis/Leukapheresis
Other name:
Hemapheresis
Summary:
The purpose of this study is to determine the response rate to the combination of folate
receptor alpha dendritic cells (FRaDCs) plus pembrolizumab in patients with advanced
ovarian, fallopian tube, or primary peritoneal cancer. Vaccines made from a person's
peptide treated white blood cells may help the body build an effective immune response to
kill tumor cells.
Detailed description:
PRIMARY OBJECTIVES:
I. To determine whether the combination of FRalphaDCs and pembrolizumab has an acceptable
toxicity profile in patients with recurrent ovarian cancer (OC). (Phase I) II. To measure
the confirmed objective response rate (ORR) to the combination of FRalphaDCs and
pembrolizumab in patients with recurrent OC. (Phase II)
SECONDARY OBJECTIVES:
I. To estimate the disease control rate (DCR-percentage of patients achieving a complete
response, partial response, or stable disease) of the combination of FRalphaDCs and
pembrolizumab in patients with recurrent OC.
II. To estimate the duration of response (DoR) in patients with recurrent OC treated with
the combination of FRalphaDCs and pembrolizumab.
III. To estimate the progression-free survival (PFS) of patients with recurrent OC
treated with the combination of FRalphaDCs and pembrolizumab.
IV. To estimate the overall survival (OS) of patients with recurrent OC treated with the
combination of FRalphaDCs and pembrolizumab.
2.25 To characterize the adverse event (AE) profile in patients with recurrent OC treated
with the combination of FRalphaDCs and pembrolizumab.
CORRELATIVE OBJECTIVES:
I. To determine whether the combination of FRalphaDCs and pembrolizumab induces an
increase in the frequency of FRalpha-specific IL-17-secreting T cells (Th17s) in patients
with recurrent OC.
II. Characterize the T cell and antibody responses to FRalpha and assess the association
between the emergence of immunity and recurrence-free (RFS).
III. To determine whether the combination of FRalphaDCs and pembrolizumab induces an
increase in the frequency of FRalpha-specific IFNgamma-secreting T cells (Th1s) in
patients with recurrent OC.
IV. To determine whether the combination of FRalphaDCs and pembrolizumab induces an
increase in the frequency of FRalpha-specific IgG antibodies in patients with recurrent
OC.
V. To determine whether the combination of FRalphaDCs and pembrolizumab induces changes
in the immune microenvironment of ovarian tumors.
OUTLINE:
Patients 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 intradermally (ID) and pembrolizumab intravenously
(IV) on study. Patients also undergo computed tomography (CT) and/or magnetic resonance
imaging (MRI) as well as blood sample collection throughout the trial. Patients undergo
biopsy on study.
Patients are followed up at 90 days after last dose, every 3 months until 24 months after
registration or until progression of disease, and then every 6 months up to 5 years after
registration.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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 (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
- 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: Patients with
platinum-sensitive recurrent OC must have either received at least two prior
courses of platinum-based chemotherapy AND/OR have a documented allergy to
carboplatin 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)
- Monocytes >= 0.25 x 10^9/L (obtained =< 15 days prior to registration)
- Total bilirubin =< 1.5 x upper limit of normal (ULN), unless patient has a
documented history of Gilbert's disease, then direct bilirubin must be =< ULN
(obtained =< 15 days prior to registration)
- Aspartate transaminase (AST) =< 3 x ULN (obtained =< 15 days prior to registration)
- Creatinine clearance >= 30 mL/min per Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) creatinine equation (obtained =< 15 days prior to
registration)
- Negative pregnancy test done =< 7 days prior to registration, for persons of
childbearing potential only
- Provide written informed consent
- Willing to provide mandatory blood and tissue specimens for correlative research
- Willing to provide archival tissue specimen for correlative research
- Willing to return to Mayo Clinic 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 whose
genotoxic, mutagenic and teratogenic effects 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 FRalphaDC product, a "wash-out" period of 3 or 1 week(s) prior
to registration will cause a gap of at least 7 or 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-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
- Known history of human immunodeficiency virus (HIV) infection NOTE: No HIV testing
is required unless mandated by local health authority
- Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active serious infections (e.g., pneumonia, sepsis) requiring
systemic therapy
- Current diagnosis or previous history of immune-related (non-infectious)
pneumonitis or interstitial lung disease that requires or required steroids
- Active autoimmune disease that required systemic treatment other than
replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroids)
=< 2 years prior to registration
- Psychiatric illness/social situations that would limit compliance with study
requirements
- Concurrent active hepatitis B (defined as HBsAg positive and/or detectable HBV
DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV
RNA) infection. EXCEPTIONS:
- For patients with evidence of hepatitis B virus (HBV) infection (hepatitis
B surface antigen [HBsAg] positive), patients must have completed at least
4 weeks of hepatitis B virus (HBV) antiviral therapy and the HBV viral
load must be undetectable at the time of registration
- Patients with a history of hepatitis C virus (HCV) are eligible if they
have an undetectable HCV viral load. Patients must have completed curative
anti-viral treatment >= 4 weeks prior to registration
- NOTE: Patients without symptoms or prior history do not require testing prior
to registration
- Other active malignancy either requiring palliative systemic therapy =< 3 years
prior to registration, or likely to require treatment in the next 2 years
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
- 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 >10 mg/day or equivalent, cyclophosphamide, azathioprine, methotrexate,
thalidomide, and anti-tumor necrosis factor [TNF]-alpha agents) =< 7 days 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
- History of allogeneic stem cell transplant
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Matthew S. Block, M.D., Ph.D.
Email:
Principal Investigator
Start date:
September 28, 2023
Completion date:
July 15, 2027
Lead sponsor:
Agency:
Mayo Clinic
Agency class:
Other
Collaborator:
Agency:
NanoPass Technologies Ltd
Agency class:
Industry
Source:
Mayo Clinic
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05920798
https://www.mayo.edu/research/clinical-trials
