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

Primary Peritoneal Carcinoma Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02485990
• Other study ID #: J15113
• Secondary ID: IRB00064379
• Status: Terminated
• Phase: Phase 1
• Start date: January 8, 2016
• Est. completion date: March 5, 2020

Study information

• Verified date: April 2021
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: March 5, 2020
• Est. primary completion date: March 5, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Primary Peritoneal Carcinoma

Intervention

Drug:
• Tremelimumab

• Olaparib

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (3)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	AstraZeneca, MedImmune LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Maximum Tolerated Dose (MTD) of tremelimumab combined with olaparib	Dose escalation (phase I) portion of the trial only.	4 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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