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About
This pilot clinical trial studies the effect of pembrolizumab and lenvatinib in treating patients with high-grade serous ovarian cancers. 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. Lenvatinib is an enzyme inhibitor that may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and lenvatinib may help to control the disease and provide an effective therapeutic option for cancer.
Full description
PRIMARY OBJECTIVE:
I. To estimate both the individual and combined effects of pembrolizumab and lenvatinib on T-cell dysfunction and proliferation in the peritoneal tumor microenvironment (p-TME) in subjects with high-grade serous ovarian cancers with peritoneal metastasis.
SECONDARY OBJECTIVES:
I. To estimate the objective response rate to pembrolizumab and lenvatinib combination in subjects with platinum-resistant high-grade serous ovarian cancer.
II. To estimate the individual and synergistic effects of pembrolizumab and lenvatinib on T-cell effector function, improved T cell memory establishment, and myeloid subpopulations in the p-TME.
EXPLORATORY OBJECTIVES:
I. To profile the dynamic changes in the immune phenotypes by dissecting the cell types and functional states of various immune cell subsets in the sequential p-TME samples using single cell ribonucleic acid sequencing (scRNAseq) and investigate changes in peritoneal immune (T-cells, B cells, natural killer [NK] cells, dendritic cells, neutrophils, tumor-associated macrophages [TAMs], myeloid-derived suppressor cells [MDSCs]) and non-immune cells (fibroblasts, tumor cells) to identify cell subsets that are associated with immune resistance and therapy response.
II. To characterize T/B cell immune repertoire and their clonotypic phenotypes in a subset of responders and non-responders using single cell T-cell receptor (TCR)/B-cell receptor (BCR) sequencing (scTCR/BCRseq) simultaneously with scRNAseq.
OUTLINE: Patients are randomized to 1 of 2 arms.
COHORT A: Beginning cycle 0, patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Beginning cycle 1, patients also receive lenvatinib orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.
COHORT B: Beginning cycle 0, patients receive lenvatinib PO QD on days 1-21. Beginning cycle 1, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 30 days, every 6 weeks for 1 year, then every 9 weeks thereafter. Patients with confirmed disease progression are followed every 12 weeks.
Enrollment
Sex
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Volunteers
Inclusion criteria
Female participants who are at least 18 years of age.
Signed written informed consent.
A histology confirming diagnosis of high grade serous ovarian/peritoneal/fallopian tube cancers and platinum-resistant disease as defined as disease progression on a platinum-containing agent or recurrent within 180 days of prior dose of a platinum-containing chemotherapeutic regimen will be enrolled in this study. Pathology must have been reviewed at MD Anderson.
A female participant is eligible to participate if at least one of the following conditions applies:
Measurable disease is present as defined by modified Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criterion, and there is disease present in the peritoneal cavity or retroperitoneal lymph nodes. Disease outside the peritoneal cavity is allowed as long as metastases are present within the peritoneal cavity or retroperitoneum.
Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal to 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the start of treatment.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Ability to understand and willingness to sign informed consent form prior to initiation of the study and any study procedures.
Participants willing to undergo intraperitoneal port placement and scheduled peritoneal fluid and peripheral blood draws.
Absolute neutrophil count (ANC) >= 1500/uL (within 10 days prior to start of study treatment)
Platelets >= 100,000/uL (within 10 days prior to start of study treatment)
Hemoglobin >= 9.0 g/dL (transfusion is allowed) (within 10 days prior to start of study treatment)
Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) >= 30 mL/min for participants with creatinine > 1.5 x ULN (within 10 days prior to start of study treatment)
Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN (within 10 days prior to start of study treatment)
Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x ULN (=< 5 x ULN for participants with liver metastases) (within 10 days prior to start of study treatment)
International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants (within 10 days prior to start of study treatment)
Exclusion criteria
Primary purpose
Allocation
Interventional model
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30 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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