This phase I/II trial studies how well pembrolizumab and carboplatin work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back (relapsed) or has not responded to previous treatment (refractory). 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. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab and carboplatin with platinum resistant chemotherapy may work better than platinum chemotherapy alone in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.
PRIMARY OBJECTIVES: I. To determine the clinical response rate of platinum chemotherapy and pembrolizumab (MK-3475) in platinum chemotherapy pretreated ovarian, fallopian tube, and primary peritoneal. II. To examine whether retreatment with platinum chemotherapy in platinum resistant ovarian, fallopian tube, and primary peritoneal cancers improves progression free survival by concurrent administration of MK-3475. SECONDARY OBJECTIVES: I. To assess the safety and tolerability of concurrent administration of MK-3475 with platinum chemotherapy in patients with platinum resistant recurrent ovarian, fallopian tube, and primary peritoneal cancers. II. To determine the relationship between PD-L1 expression and response to the combination of MK-3475 and platinum. III. To assess the overall survival of patients treated with the combination of MK-3475 and platinum. EXPLORATORY OBJECTIVE: I. To explore whether treatment with MK-3475 and platinum alters soluble factors in sera, peripheral immune responses and immune cell profile. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, every 6 months for 1 year, and then every 12 weeks thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
29
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Response Rate (RR) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI/CT scans: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: 6 months
Progression-free Survival (PFS) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% confidence intervals (CIs) at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control PFS will be conducted by examining whether the 95% confidence internal covers the historical control proportions. Progression-free survival (PFS) is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Participants are evaluated by RECIST1.1 to determine if/when a participant's disease has progressed defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: 6 months
Count of Adverse Events Evaluated by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
The safety evaluation of the population included all patients who received at least one dose of study medication. The descriptions and grading scales found in the revised NCI CTCAE version 4.0 will be utilized for adverse event reporting where Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms Grade 2 Moderate; minimal Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care of activity of daily living Grade 4 Life-threatening consequences; urgent intervention indicated Grade 5 Death related to AE
Time frame: Up to 3.5 years
Number of Participants That Were PD-L1 Positive Based On PD-L1 Expression of Primary Tumor Blocks Assessed by Immunohistochemical Staining
PD-L1 antibody-stained archival tumor was evaluated by a board-certified pathologist and given a modified proportion score (MPS), or the overall percent of positive cells expressing PD-L1, and a MPS ≥ 5% was defined as PD-L1 positive.
Time frame: Up to 3.5 years
Overall Survival (OS)
Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control OS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.
Time frame: Up to 3.5 years
Best Overall Response (BOR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI/CT scans: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: Up to 3.5 years
Progression-free Survival (PFS) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control PFS will be conducted by examining whether the 95% confidence internal covers the historical control proportions. Progression-free survival (PFS) is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Participants are evaluated by RECIST1.1 to determine if/when a participant's disease has progressed defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: Up to 3.5 years
Immune-related Best Overall Response (BOR) Assessed Using irRECIST (Immune-related Response Evaluation Criteria In Solid Tumors) Derived From Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI/CT scans: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: Up to 3.5 years
Immune-related Progression-free Survival (PFS) Using irRECIST (Immune-related Response Evaluation Criteria In Solid Tumors) Derived From Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Progression-free survival (PFS) is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Participants are evaluated by RECIST1.1 to determine if/when a participant's disease has progressed defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: Up to 3.5 years
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