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

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)

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).

Study Overview

• Status: Terminated
• Conditions: Primary Peritoneal Carcinoma
• Intervention / Treatment: Drug: Tremelimumab; Drug: Olaparib

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

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
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
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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: AstraZeneca; MedImmune LLC
• Investigators: Principal Investigator: Stéphanie Gaillard, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2016
• Primary Completion (Actual): March 5, 2020
• Study Completion (Actual): March 5, 2020

Study Registration Dates

• First Submitted: June 26, 2015
• First Submitted That Met QC Criteria: June 29, 2015
• First Posted (Estimate): June 30, 2015

Study Record Updates

• Last Update Posted (Actual): April 12, 2021
• Last Update Submitted That Met QC Criteria: April 9, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Fallopian Tube; EOC; Epithelial Ovarian
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Olaparib; Tremelimumab
• Other Study ID Numbers: J15113; IRB00064379 (Other Identifier: JHM IRB)