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

NCT02485990 | Terminated Phase 1 DMC

• 2 other identifiers: J15113IRB00064379
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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).

Conditions

Primary Peritoneal Carcinoma

Keywords

Fallopian Tube; Epithelial Ovarian; EOC

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (9)

• Progression Free Survival (PFS) Rate at 6 months by RECIST

  6 months

• Progression Free Survival (PFS) Rate at 6 months by irRECIST

  6 months

• Objective Response Rate (ORR) by RECIST

  4 years

• Objective Response Rate (ORR) by irRECIST

  4 years

• Duration of Response by RECIST

  4 years

Study Arms (3)

Arm A: Tremelimumab Alone

EXPERIMENTAL

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

Arm B1: DESE Tremelimumab and Olaparib

EXPERIMENTAL

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

Arm B2: Tremelimumab and Olaparib

EXPERIMENTAL

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

Interventions

Tremelimumab DRUG

Arm A: Tremelimumab Alone; Arm B1: DESE Tremelimumab and Olaparib; Arm B2: Tremelimumab and Olaparib

Olaparib DRUG

Also known as: LYNPARZA

Arm B1: DESE Tremelimumab and Olaparib; Arm B2: Tremelimumab and Olaparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form
• Age ≥ 18 years
• Recurrent or persistent EOC (epithelial ovarian, fallopian tube or primary peritoneal carcinoma)
• Have archival tissue or willingness to undergo a tumor biopsy
• Have measurable disease
• Have had one prior taxane-platinum-based chemotherapeutic regimen
• 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
• Have received hormonal therapy
• ECOG Performance Status of 0 to 1
• Ability to take oral medications
• HIV, HTLV-1, HBV, and HCV negative
• Adequate organ and bone marrow function as defined by study-specified laboratory tests
• Normal blood coagulation parameters
• Life expectancy greater than 16 weeks
• Must use acceptable form of birth control through the study and for 28 days after final dose of study drug

You may not qualify if:

• Prior therapy with an anti-CTLA-4 antibody or PARP inhibitor
• Active infection requiring antibiotics
• Active autoimmune disease
• Active and uncontrolled intercurrent illness
• History of other cancers within the past 5 years
• Systemically active steroid use
• Receiving systemic chemotherapy or radiotherapy within 4 weeks prior to the first dose of study drug
• Use of ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir
• Requirement for chronic parenteral hydration/nutrition
• Vaccination with live attenuated vaccine within 1 month prior to first dose of study drug
• Patients with untreated brain metastases, treated brain metastases that are not stable, leptomeningeal disease, or seizures uncontrolled with standard medical therapy
• Patients with myelodysplastic syndrome/acute myeloid leukaemia
• History of diverticulitis
• History of bleeding disorder or diathesis.
• Serious or nonhealing wound, ulcer, bone fracture, or osteonecrosis of the jaw

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• AstraZeneca: collaborator
• MedImmune LLC: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Interventions

tremelimumab; olaparib

Study Officials

• Stephanie Gaillard, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2015
• First Posted: June 30, 2015
• Study Start: January 8, 2016
• Primary Completion: March 5, 2020
• Study Completion: March 5, 2020
• Last Updated: April 12, 2021

Record last verified: 2021-04

Locations

US (1)