Back to resultsStudy of Tremelimumab Alone or Combined With Olaparib for Patients With Persistent EOC (Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma)
Primary Purpose
Primary Peritoneal Carcinoma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Tremelimumab
Olaparib
Sponsored by
About this trial
This is an interventional treatment trial for Primary Peritoneal Carcinoma focused on measuring Fallopian Tube, Epithelial Ovarian, EOC
Eligibility Criteria
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
Sites / Locations
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Arm A: Tremelimumab Alone
Arm B1: DESE Tremelimumab and Olaparib
Arm B2: Tremelimumab and Olaparib
Arm Description
25 patients will receive tremelimumab alone at 10 mg/kg IV every 4 weeks for 7 doses then every 12 weeks until disease progression.
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.
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).
Outcomes
Primary Outcome Measures
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.
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.
Maximum Tolerated Dose (MTD) of tremelimumab combined with olaparib
Dose escalation (phase I) portion of the trial only.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT02485990
First Posted
June 26, 2015
Last Updated
April 9, 2021
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
AstraZeneca, MedImmune LLC
1. Study Identification
Unique Protocol Identification Number
NCT02485990
Brief Title
Study of Tremelimumab Alone or Combined With Olaparib for Patients With Persistent EOC (Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Terminated
Why Stopped
Withdrawal of sponsor support
Study Start Date
January 8, 2016 (Actual)
Primary Completion Date
March 5, 2020 (Actual)
Study Completion Date
March 5, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
AstraZeneca, MedImmune LLC
4. Oversight
Data Monitoring Committee
Yes
5. 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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Peritoneal Carcinoma
Keywords
Fallopian Tube, Epithelial Ovarian, EOC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: Tremelimumab Alone
Arm Type
Experimental
Arm Description
25 patients will receive tremelimumab alone at 10 mg/kg IV every 4 weeks for 7 doses then every 12 weeks until disease progression.
Arm Title
Arm B1: DESE Tremelimumab and Olaparib
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm B2: Tremelimumab and Olaparib
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Tremelimumab
Intervention Type
Drug
Intervention Name(s)
Olaparib
Other Intervention Name(s)
LYNPARZA
Primary Outcome Measure Information:
Title
Adverse events as a measure of the safety and tolerability profile of tremelimumab in combination with olaparib
Description
Number of participants experiencing study drug-related dose limiting toxicities (DLTs). Dose escalation (phase I) portion of the trial only.
Time Frame
4 years
Title
Fold change from baseline in the ratio of peripheral CD4+ICOShi T cells and Regulatory T cells
Description
Dose escalation (phase I) portion of the trial only.
Time Frame
4 years
Title
Maximum Tolerated Dose (MTD) of tremelimumab combined with olaparib
Description
Dose escalation (phase I) portion of the trial only.
Time Frame
4 years
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS) Rate at 6 months by RECIST
Description
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.
Time Frame
6 months
Title
Progression Free Survival (PFS) Rate at 6 months by irRECIST
Description
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.
Time Frame
6 months
Title
Objective Response Rate (ORR) by RECIST
Description
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.
Time Frame
4 years
Title
Objective Response Rate (ORR) by irRECIST
Description
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.
Time Frame
4 years
Title
Duration of Response by RECIST
Description
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.
Time Frame
4 years
Title
Duration of Response by irRECIST
Description
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.
Time Frame
4 years
Title
Disease Control Rate (DCR)
Description
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.
Time Frame
4 years
Title
Progression-Free Survival (PFS)
Description
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.
Time Frame
4 years
Title
Overall Survival (OS)
Description
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.
Time Frame
4 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephanie Gaillard, MD
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of Tremelimumab Alone or Combined With Olaparib for Patients With Persistent EOC (Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma)
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