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

Phase 1TerminatedNCT02485990

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins24 enrolled

Overview

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).

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Primary Peritoneal Carcinoma

Interventions

TremelimumabDRUG

OlaparibDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 4 years

Maximum Tolerated Dose (MTD) of tremelimumab combined with olaparib

Dose escalation (phase I) portion of the trial only.

Time frame: 4 years

Secondary Outcomes

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.

Time frame: 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.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.