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

• ClinicalTrials.gov Identifier: NCT02485990
• Recruitment Status: Terminated
• First Posted: June 30, 2015
• Last Update Posted: April 12, 2021
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: AstraZeneca; MedImmune LLC
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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 (Clinical Trial)
• 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: January 8, 2016
• Actual Primary Completion Date: March 5, 2020
• Actual Study Completion Date: March 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 Name: 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 Name: LYNPARZA

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Progression Free Survival (PFS) Rate at 6 months by RECIST [ Time Frame: 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.
2. Progression Free Survival (PFS) Rate at 6 months by irRECIST [ Time Frame: 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.
3. Objective Response Rate (ORR) by RECIST [ Time Frame: 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.
4. Objective Response Rate (ORR) by irRECIST [ Time Frame: 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.
5. Duration of Response by RECIST [ Time Frame: 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.
6. Duration of Response by irRECIST [ Time Frame: 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.
7. Disease Control Rate (DCR) [ Time Frame: 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.
8. Progression-Free Survival (PFS) [ Time Frame: 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.
9. Overall Survival (OS) [ Time Frame: 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

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

Criteria

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

Contacts and Locations

Locations

United States, Maryland

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States, 21231

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

AstraZeneca

MedImmune LLC

Investigators

• Principal Investigator: Stephanie Gaillard, MD; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

More Information

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT02485990
• Other Study ID Numbers: J15113; IRB00064379 ( Other Identifier: JHM IRB )
• First Posted: June 30, 2015
• Last Update Posted: April 12, 2021
• Last Verified: April 2021

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:

Fallopian Tube; Epithelial Ovarian; EOC

Additional relevant MeSH terms:

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Olaparib; Tremelimumab; Poly(ADP-ribose) Polymerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents