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)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Adverse events as a measure of the safety and tolerability profile of tremelimumab in combination with olaparib
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Willing and able to comply with study procedures
排除标准
- •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
- •Major surgical procedure within 28 days of study enrollment, or anticipated while on study.
- •Pregnant or breast feeding woman
研究组 & 干预措施
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.
干预措施: Tremelimumab (Drug)
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.
干预措施: Tremelimumab (Drug)
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.
干预措施: Olaparib (Drug)
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).
干预措施: Tremelimumab (Drug)
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).
干预措施: Olaparib (Drug)
结局指标
主要结局
Adverse events as a measure of the safety and tolerability profile of tremelimumab in combination with olaparib
时间窗: 4 years
Number of participants experiencing study drug-related dose limiting toxicities (DLTs). Dose escalation (phase I) portion of the trial only.
Maximum Tolerated Dose (MTD) of tremelimumab combined with olaparib
时间窗: 4 years
Dose escalation (phase I) portion of the trial only.
Fold change from baseline in the ratio of peripheral CD4+ICOShi T cells and Regulatory T cells
时间窗: 4 years
Dose escalation (phase I) portion of the trial only.
次要结局
- 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)
- Disease Control Rate (DCR)(4 years)
- Progression-Free Survival (PFS)(4 years)
- Overall Survival (OS)(4 years)
- Progression Free Survival (PFS) Rate at 6 months by RECIST(6 months)
- Duration of Response by irRECIST(4 years)
- Duration of Response by RECIST(4 years)