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

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Terminated

CT.gov ID

NCT02485990

Collaborator

AstraZeneca (Industry), MedImmune LLC (Industry)

Enrollment

Location

Arms

49.9

Actual Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Primary Peritoneal Carcinoma	Drug: Tremelimumab Drug: Olaparib	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Jan 8, 2016

Actual Primary Completion Date :

Mar 5, 2020

Actual Study Completion Date :

Mar 5, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Tremelimumab Alone 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
Experimental: Arm B1: DESE Tremelimumab and Olaparib 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 Drug: Olaparib Other Names: LYNPARZA
Experimental: Arm B2: Tremelimumab and Olaparib 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 Drug: Olaparib Other Names: LYNPARZA

Arm

Intervention/Treatment

Experimental: Arm A: Tremelimumab Alone

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

Experimental: Arm B1: DESE Tremelimumab and Olaparib

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

Drug: Olaparib

Other Names:

LYNPARZA

Experimental: Arm B2: Tremelimumab and Olaparib

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

Drug: Olaparib

Other Names:

LYNPARZA

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Progression Free Survival (PFS) Rate at 6 months by RECIST [6 months]
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.
Progression Free Survival (PFS) Rate at 6 months by irRECIST [6 months]
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.
Objective Response Rate (ORR) by RECIST [4 years]
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.
Objective Response Rate (ORR) by irRECIST [4 years]
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.
Duration of Response by RECIST [4 years]
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.
Duration of Response by irRECIST [4 years]
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.
Disease Control Rate (DCR) [4 years]
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.
Progression-Free Survival (PFS) [4 years]
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.
Overall Survival (OS) [4 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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