Primary Peritoneal Carcinoma
Conditions
Keywords
Fallopian Tube, Epithelial Ovarian, EOC
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.
Interventions
DRUGTremelimumab
DRUGOlaparib
Sponsors
AstraZeneca
MedImmune LLC
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent form 2. Age ≥ 18 years 3. Recurrent or persistent EOC (epithelial ovarian, fallopian tube or primary peritoneal carcinoma) 4. Have archival tissue or willingness to undergo a tumor biopsy 5. Have measurable disease 6. Have had one prior taxane-platinum-based chemotherapeutic regimen 7. 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 8. Have received hormonal therapy 9. ECOG Performance Status of 0 to 1 10. Ability to take oral medications 11. HIV, HTLV-1, HBV, and HCV negative 12. Adequate organ and bone marrow function as defined by study-specified laboratory tests 13. Normal blood coagulation parameters 14. Life expectancy greater than 16 weeks 15. Must use acceptable form of birth control through the study and for 28 days after final dose of study drug 16. Willing and able to comply with study procedures
Exclusion criteria
1. Prior therapy with an anti-CTLA-4 antibody or PARP inhibitor 2. Active infection requiring antibiotics 3. Active autoimmune disease 4. Active and uncontrolled intercurrent illness 5. History of other cancers within the past 5 years 6. Systemically active steroid use 7. Receiving systemic chemotherapy or radiotherapy within 4 weeks prior to the first dose of study drug 8. Use of ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir 9. Requirement for chronic parenteral hydration/nutrition 10. Vaccination with live attenuated vaccine within 1 month prior to first dose of study drug 11. Patients with untreated brain metastases, treated brain metastases that are not stable, leptomeningeal disease, or seizures uncontrolled with standard medical therapy 12. Patients with myelodysplastic syndrome/acute myeloid leukaemia 13. History of diverticulitis 14. History of bleeding disorder or diathesis. 15. Serious or nonhealing wound, ulcer, bone fracture, or osteonecrosis of the jaw 16. Major surgical procedure within 28 days of study enrollment, or anticipated while on study. 17. Pregnant or breast feeding woman
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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) | 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. |
| 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) 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. |
Countries
United States
Outcome results
None listed