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

Johns Hopkins Medicine

Status and phase: Terminated; Phase 1

Conditions: Primary Peritoneal Carcinoma

Treatments: Drug: Tremelimumab; Drug: Olaparib

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02485990

J15113

IRB00064379 (Other Identifier)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 24 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 3 patient groups

Arm A: Tremelimumab Alone

Experimental group

Description:

25 patients will receive tremelimumab alone at 10 mg/kg IV every 4 weeks for 7 doses then every 12 weeks until disease progression.

Treatment:

Drug: Tremelimumab

Arm B1: DESE Tremelimumab and Olaparib

Experimental group

Description:

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.

Treatment:

Drug: Olaparib

Drug: Tremelimumab

Arm B2: Tremelimumab and Olaparib

Experimental group

Description:

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).

Treatment:

Drug: Olaparib

Drug: Tremelimumab