A Phase I/II Study of ABT-888 in Combination With 5-fluorouracil and Oxaliplatin (Modified FOLFOX-6) in Patients With Metastatic Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Phase 1: Number of Dose Limiting Toxicities
研究概览
简要总结
People are being asked to participate in this study who have metastatic pancreatic cancer (cancer that has spread to other parts of the body).
The purpose of this study is to test the efficacy (effectiveness) of a new combination of drugs, ABT-888 and mFOLFOX-6 (modified 5-Fluorouracil and Oxaliplatin) for patients with metastatic pancreatic cancer.
ABT-888 inhibits an enzyme called "PARP" which helps to fix damaged DNA. By inhibiting this enzyme, ABT-888 prevents cancer cells from repairing the damage caused by the mFOLFOX-6, and will hopefully increase the killing of cancer cells, thus decreasing the tumors in your body.
详细描述
This is a single arm, open-label Phase I/II study to evaluate the clinical activity of the novel inhibitor of Poly(ADP-ribose) polymerase (PARP), ABT-888 with modified FOLFOX-6 (5-Fluorouracil plus oxaliplatin) in patients with metastatic pancreatic cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Histologically proven pancreatic adenocarcinoma with measurable disease
- •A known BRCA-associate genetic mutation OR family history suggesting of a breast or ovarian cancer syndrome, as defined by one or more of the following:
- •Personal or known family history of a deleterious (or indeterminate) mutation in the BRCA1, BRCA2, PALBB2, or one of the FANC genes.
- •Personal history of breast cancer and one or more of the following:
- •Diagnosed ≤ 45 years old
- •Diagnosed at any age with ≥1 1st, 2nd, or 3rd degree relative with breast cancer ≤ 50 years old and/or ≥1st, 2nd, or 3rd relative with epithelial ovarian cancer at any age
- •Two primary breast cancer with the first diagnosed at ≤ 50 years old
- •Diagnosed ≤ 60 years old with triple negative breast cancer
- •Diagnosed at any age with ≥2 1st, 2nd, or 3rd degree relatives with breast cancer at any age
- •Diagnosed at any age with ≥2 1st, 2nd, or 3rd degree relatives with pancreatic cancer or aggressive prostate cancer (Gleason score ≥7) at any age
- •1st, 2nd, or 3rd degree male relative with breast cancer
- •Ashkenazi Jewish descent
- •Personal history of epithelial ovarian cancer
- •Personal history of male breast cancer
- •Personal history of pancreatic cancer and ≥2 1st, 2nd, or 3rd degree relatives with breast, epitherlial ovarian, pancreatic, or aggressive prostate cancer (Gleason score ≥7) at any age
- •Age >= 18 years
- •ECOG performance status 0-2
- •Subjects with no brain metastases or a history of previously treated brain metastases who have been treated with surgery or stereotactic radiosurgery at least 4 weeks prior to enrollment and have a baseline MRI that shows no evidence of intercranial disease and have not had treatment with steroids within 1 week of study enrollment.
- •Subjects may have received any number of prior therapies except prior therapy with a PARP inhibitor
- •At least 14 days must have passed since all prior anti-cancer therapy
- •At least 28 days must have passed since any prior antibody-based therapies
- •At least 28 days must have passed since any prior investigational agent
- •All patients must have completely recovered from all transient side effects related to prior therapies and any side effects that are expected to be more durable or permanent must have resolved to Grade 1
- •Adequate hepatic, bone marrow and renal function
- •Partial thromboplastin time must be </= 2 X upper limit of institution's normal range and INR <
- •Subjects on an anticoagulant must have a PTT </= 5 X upper limit of institution's normal range and INR <
- •Life expectancy > 12 weeks
- •Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment
- •Subject must be capable of understanding and complying with parameters as outlined in protocol and able to sign and date the informed consent form
- •Patients must have fully recovered from all effects of surgery.
排除标准
- •Active severe infection, or known chronic infection with HIV, Hepatitis B virus or Hepatitis C virus
- •Cardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 months
- •Life-threatening visceral disease or other severe concurrent disease
- •Women who are pregnant or breast-feeding
- •Anticipated survival under 3 months
- •The subject has had another active malignancy within the past 5 years except for cervical cancer in situ, in situ carcinoma of the bladder, or non-melanoma carcinoma of the skin.
- •Active uncontrolled infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris or cardiac arrhythmia
- •Psychiatric illness/ social situation that would limit compliance with study requirements
研究组 & 干预措施
Phase 1: ABT-888 40mg (Cohort 1)
ABT-888 orally at 40mg twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6 with 5-FU bolus mFOLFOX-6: Oxaliplatin 85 mg/M2 IV on Day 1 Leucovorin 400 mg/m2 IV on Day 1; 5-FU 400 mg/m2 IV bolus followed by 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: ABT-888 (Drug)
Phase 1: ABT-888 40mg (Cohort 1)
ABT-888 orally at 40mg twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6 with 5-FU bolus mFOLFOX-6: Oxaliplatin 85 mg/M2 IV on Day 1 Leucovorin 400 mg/m2 IV on Day 1; 5-FU 400 mg/m2 IV bolus followed by 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: mFOLFOX-6 (Drug)
Phase 1: ABT-888 60 mg (Cohort 2)
ABT-888 orally at 60mg with mFOLFOX-6 twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6: Oxaliplatin 85 mg/m2 IV on Day 1; Leucovorin 400 mg/m2 IV on Day 1; 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: ABT-888 (Drug)
Phase 1: ABT-888 60 mg (Cohort 2)
ABT-888 orally at 60mg with mFOLFOX-6 twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6: Oxaliplatin 85 mg/m2 IV on Day 1; Leucovorin 400 mg/m2 IV on Day 1; 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: mFOLFOX-6 (Drug)
Phase 1: ABT-888 80 mg (Cohort 3)
ABT-888 orally at 80mg with mFOLFOX-6 twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6: Oxaliplatin 85 mg/m2 IV on Day 1; Leucovorin 400 mg/m2 IV on Day 1; 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: ABT-888 (Drug)
Phase 1: ABT-888 80 mg (Cohort 3)
ABT-888 orally at 80mg with mFOLFOX-6 twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6: Oxaliplatin 85 mg/m2 IV on Day 1; Leucovorin 400 mg/m2 IV on Day 1; 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: mFOLFOX-6 (Drug)
Phase 1: ABT-888 100 mg (Cohort 4)
ABT-888 orally at 100mg with mFOLFOX-6 twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6: Oxaliplatin 85 mg/m2 IV on Day 1; Leucovorin 400 mg/m2 IV on Day 1; 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: ABT-888 (Drug)
Phase 1: ABT-888 100 mg (Cohort 4)
ABT-888 orally at 100mg with mFOLFOX-6 twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6: Oxaliplatin 85 mg/m2 IV on Day 1; Leucovorin 400 mg/m2 IV on Day 1; 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: mFOLFOX-6 (Drug)
Phase 1: ABT-888 150 mg (Cohort 5)
ABT-888 orally at 150mg with mFOLFOX-6 twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6: Oxaliplatin 85 mg/m2 IV on Day 1; Leucovorin 400 mg/m2 IV on Day 1; 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: ABT-888 (Drug)
Phase 1: ABT-888 150 mg (Cohort 5)
ABT-888 orally at 150mg with mFOLFOX-6 twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6: Oxaliplatin 85 mg/m2 IV on Day 1; Leucovorin 400 mg/m2 IV on Day 1; 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: mFOLFOX-6 (Drug)
Phase 1: ABT-888 200 mg (Cohort 6)
ABT-888 orally at 200mg with mFOLFOX-6 twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6: Oxaliplatin 85 mg/m2 IV on Day 1; Leucovorin 400 mg/m2 IV on Day 1; 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: ABT-888 (Drug)
Phase 1: ABT-888 200 mg (Cohort 6)
ABT-888 orally at 200mg with mFOLFOX-6 twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6: Oxaliplatin 85 mg/m2 IV on Day 1; Leucovorin 400 mg/m2 IV on Day 1; 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: mFOLFOX-6 (Drug)
Phase 1: ABT-888 250 mg (Cohort 7)
ABT-888 orally at 250mg with mFOLFOX-6 twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6: Oxaliplatin 85 mg/m2 IV on Day 1; Leucovorin 400 mg/m2 IV on Day 1; 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: ABT-888 (Drug)
Phase 1: ABT-888 250 mg (Cohort 7)
ABT-888 orally at 250mg with mFOLFOX-6 twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6: Oxaliplatin 85 mg/m2 IV on Day 1; Leucovorin 400 mg/m2 IV on Day 1; 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: mFOLFOX-6 (Drug)
Phase 1: ABT-888 300 mg (Cohort 8)
ABT-888 orally at 300mg with mFOLFOX-6 twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6: Oxaliplatin 85 mg/m2 IV on Day 1; Leucovorin 400 mg/m2 IV on Day 1; 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: ABT-888 (Drug)
Phase 1: ABT-888 300 mg (Cohort 8)
ABT-888 orally at 300mg with mFOLFOX-6 twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6: Oxaliplatin 85 mg/m2 IV on Day 1; Leucovorin 400 mg/m2 IV on Day 1; 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: mFOLFOX-6 (Drug)
Phase 2: ABT-888 at Recommended phase 2 dose (200mg)
ABT-888 orally at 200mg with mFOLFOX-6 twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6: Oxaliplatin 85 mg/m2 IV on Day 1; Leucovorin 400 mg/m2 IV on Day 1; 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: ABT-888 (Drug)
Phase 2: ABT-888 at Recommended phase 2 dose (200mg)
ABT-888 orally at 200mg with mFOLFOX-6 twice a day for Days 1-7 of each 14-day cycle with mFOLFOX-6: Oxaliplatin 85 mg/m2 IV on Day 1; Leucovorin 400 mg/m2 IV on Day 1; 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
干预措施: mFOLFOX-6 (Drug)
结局指标
主要结局
Phase 1: Number of Dose Limiting Toxicities
时间窗: 28 days
Protocol defined events that are definitely, possibly or probably related to one or both agents and have occurred in the first cycle of therapy. Applies only to patients in the Phase I portion of the study.
Phase II: Objective Response Rate (ORR)
时间窗: 6 months
Number of Participants in Phase II with a Complete response and Partial response as determined by RECIST 1.1.
次要结局
- Disease Control Rate (DCR)(6 months)
- Progression Free Survival (PFS)(up to 114 months)
- Overall Survival(up to 114 months)