Study of Tremelimumab Alone or Combined With Olaparib for Patients With Persistent EOC (Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma)

Study Overview
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Brief Summary
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This study will be looking at what dose of tremelimumab and olaparib is safe and effective in patients with persistent EOC (Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma).

Detailed Description
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This clinical trial was initially intended to be a Phase 1/2 trial, but the trial never moved forward to Phase 2 prior to termination.

Official Title
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An Open Label Dose Escalation/Expansion Study of Tremelimumab Alone or Combined With Olaparib for Recurrent or Persistent EOC (Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma)

Conditions
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Primary Peritoneal Carcinoma

Intervention / Treatment
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* Drug: Tremelimumab
* Drug: Olaparib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form Age ≥ 18 years Recurrent or persistent EOC (epithelial ovarian, fallopian tube or primary peritoneal carcinoma) Have archival tissue or willingness to undergo a tumor biopsy Have measurable disease Have had one prior taxane-platinum-based chemotherapeutic regimen Have had a treatment-free interval following platinum-based therapy of less than 12 months, have progressed during platinum-based therapy, or had persistent disease after a platinum-based regimen Have received hormonal therapy ECOG Performance Status of 0 to 1 Ability to take oral medications HIV, HTLV-1, HBV, and HCV negative Adequate organ and bone marrow function as defined by study-specified laboratory tests Normal blood coagulation parameters Life expectancy greater than 16 weeks Must use acceptable form of birth control through the study and for 28 days after final dose of study drug Willing and able to comply with study procedures Exclusion Criteria: Prior therapy with an anti-CTLA-4 antibody or PARP inhibitor Active infection requiring antibiotics Active autoimmune disease Active and uncontrolled intercurrent illness History of other cancers within the past 5 years Systemically active steroid use Receiving systemic chemotherapy or radiotherapy within 4 weeks prior to the first dose of study drug Use of ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir Requirement for chronic parenteral hydration/nutrition Vaccination with live attenuated vaccine within 1 month prior to first dose of study drug Patients with untreated brain metastases, treated brain metastases that are not stable, leptomeningeal disease, or seizures uncontrolled with standard medical therapy Patients with myelodysplastic syndrome/acute myeloid leukaemia History of diverticulitis History of bleeding disorder or diathesis. Serious or nonhealing wound, ulcer, bone fracture, or osteonecrosis of the jaw Major surgical procedure within 28 days of study enrollment, or anticipated while on study. Pregnant or breast feeding woman

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Tremelimumab Alone<br>25 patients will receive tremelimumab alone at 10 mg/kg IV every 4 weeks for 7 doses then every 12 weeks until disease progression. | Drug: Tremelimumab<br> <br> |
| Experimental: Arm B1: DESE Tremelimumab and Olaparib<br>18 patients will receive tremelimumab (3 or 10 mg/kg IV) every 4 weeks for 7 doses then every 12 weeks and olaparib (150 or 300 mg orally twice a day) until disease progression. | Drug: Tremelimumab<br> <br> Drug: Olaparib<br> <br> * Other names: LYNPARZA;|
| Experimental: Arm B2: Tremelimumab and Olaparib<br>25 patients will receive tremelimumab (every 4 weeks for 7 doses then every 12 weeks) and olaparib (daily) until disease progression. Dose of tremelimumab and olaparib will be determined during the DESE (Arm B1). | Drug: Tremelimumab<br> <br> Drug: Olaparib<br> <br> * Other names: LYNPARZA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events as a measure of the safety and tolerability profile of tremelimumab in combination with olaparib | Number of participants experiencing study drug-related dose limiting toxicities (DLTs). Dose escalation (phase I) portion of the trial only. | 4 years | 
| Fold change from baseline in the ratio of peripheral CD4+ICOShi T cells and Regulatory T cells | Dose escalation (phase I) portion of the trial only. | 4 years | 
| Maximum Tolerated Dose (MTD) of tremelimumab combined with olaparib | Dose escalation (phase I) portion of the trial only. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) Rate at 6 months by RECIST | PFS rate is defined as the percentage of patients with disease progression (PD or relapse from CR as assessed using RECIST 1.1 criteria) or death due to any cause at 6 months. Per RECIST 1.1 criteria, Complete Response (CR) = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve. | 6 months | 
| Progression Free Survival (PFS) Rate at 6 months by irRECIST | PFS rate is defined as the percentage of patients with disease progression (irPD or relapse from irCR as assessed using irRECIST criteria) or death due to any cause at 6 months. Per irRECIST criteria, irCR = disappearance of all lesions, irPR is =>30% decrease in tumor burden, irPD is >20% increase in tumor burden compared with nadir, irSD is <30% decrease in tumor burden compared with baseline cannot be established nor <20% increase compared with nadir. Estimation based on the Kaplan-Meier curve. | 6 months | 
| Objective Response Rate (ORR) by RECIST | Objective Response Rate (ORR) is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. Per RECIST 1.1 criteria, CR = disappearance of all target lesions and PR is =>30% decrease in sum of diameters of target lesions. | 4 years | 
| Objective Response Rate (ORR) by irRECIST | Objective Response Rate (irORR) is defined as the percentage of patients achieving a complete response (irCR) or partial response (irPR) based on irRECIST criteria. Per irRECIST criteria, irCR = disappearance of all lesions and irPR is =>30% decrease in tumor burden. | 4 years | 
| Duration of Response by RECIST | Number of months from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or progressive disease or death is documented. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, and PD is >20% increase in sum of diameters of target lesions. | 4 years | 
| Duration of Response by irRECIST | Number of months from the start date of irPR or irCR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or progressive disease or death is documented. Per irRECIST criteria, irCR = disappearance of all lesions, irPR is =>30% decrease in tumor burden, and irPD is is >20% increase in tumor burden compared with nadir. | 4 years | 
| Disease Control Rate (DCR) | DCR is defined as the number of patients achieving a complete response (CR) or partial response (PR) or stable disease (SD) based on RECIST 1.1 criteria at any time during the study. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, PD is >20% increase in sum of diameters of target lesions, SD is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve. | 4 years | 
| Progression-Free Survival (PFS) | PFS is defined as the number of patients with disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve. | 4 years | 
| Overall Survival (OS) | OS will be measured from date of first dose until death or end of followup (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve. | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fallopian Tube, Epithelial Ovarian, EOC