A Phase I Study of SGI-110 Combined With Irinotecan Followed by a Randomized Phase II Study of SGI-110 Combined With Irinotecan Versus Regorafenib or TAS-102 in Previously Treated Metastatic Colorectal Cancer Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 118
- 试验地点
- 4
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
This is a phase I/II study of the combination of Guadecitabine (SGI-110) and previously treated metastatic colorectal cancer patients. This study will be conducted in two components. First, patients will be enrolled in a phase I study of SGI-110 combined with irinotecan in a standard 3+3 design. After the maximum tolerated dose (MTD) is determined, patients will subsequently be enrolled in a 2:1 randomized phase II study of SGI-110 and irinotecan versus the standard of care regorafenib or Lonsurf (TAS-102).
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
- •Histologically or cytologically confirmed adenocarcinoma of the colon or rectum
- •Phase I only: patients with biopsiable disease amenable to having two research biopsies.
- •Have measurable disease
- •Phase II only: progressed while receiving irinotecan therapy in the metastatic setting. There are no limitations on number of prior therapies in the metastatic setting.
- •Life expectancy of greater than 12 weeks.
- •Eastern Cooperative Oncology Group (ECOG) performance status <1
- •Normal organ and marrow function as defined by study-specified laboratory tests
- •Must use adequate contraception through the study and for 3 months after last dose of study drug.
排除标准
- •Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) of first dose of study drug or who have not recovered from treatment-related adverse events
- •Receiving any other investigational agents
- •Participants with known brain metastases
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to irinotecan, decitabine or SGI-
- •Received prior therapy with any hypomethylating agents.
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Pregnant or nursing women
- •History of a different malignancy are ineligible with exceptions (disease-free for at least 5 years with low risk for recurrence, cervical cancer in situ, definitively treated early stage prostate cancer, definitively treated breast ductal or lobular carcinoma in situ, and basal cell or squamous cell carcinoma of the skin).
- •HIV-positive individuals on combination antiretroviral therapy
- •Phase II only: previous treatment with regorafenib and TAS-
- •If patients have previously received either regorafenib OR TAS-102, they must be able to receive the alternate regimen if randomized to standard of care (Arm B).
- •Hospitalization for an acute medical issue within 4 weeks prior to screening visit
- •Symptomatic bowel obstruction within 6 months prior to enrollment, Patients who undergo surgical correction of obstructing lesion will be eligible within 6 months.
研究组 & 干预措施
Phase 1: Dose Escalation
Subjects receive SGI-110 on days 1-5 and irinotecan on days 8 and 15 of each 28-day cycle.
Various doses of SGI-110 are tested to determine the maximum tolerated dose in combination with irinotecan.
干预措施: SGI-110 Dose Escalation (Drug)
Phase 2: Arm A SGI-110 + irinotecan
Subjects receive SGI-110 on days 1-5 and irinotecan on days 8 and 15 of each 28-day cycle.
Growth factor support (filgrastim and peg-filgrastim) is given during cycle 1 with option to give additional growth factor support at subsequent cycles per clinician judgement.
干预措施: SGI-110 (Drug)
Phase 2: Arm A SGI-110 + irinotecan
Subjects receive SGI-110 on days 1-5 and irinotecan on days 8 and 15 of each 28-day cycle.
Growth factor support (filgrastim and peg-filgrastim) is given during cycle 1 with option to give additional growth factor support at subsequent cycles per clinician judgement.
干预措施: Irinotecan (Drug)
Phase 2: Arm B regorafenib or TAS-102
Subjects received either regorafenib or TAS-102 based on physician and patient preference. Subjects that had received one of these standard of care drugs (regorafenib or TAS-102) prior to enrollment received the other on study.
Regorafenib taken daily from days 1-21 of each 28-day cycle or TAS-102 taken twice daily on days 1-5 and 8-12 of each 28-day cycle.
Subjects who had disease progression on Arm B were given the option to receive Arm A study drugs after a 14 day wash-out period.
干预措施: Regorafenib (Drug)
Phase 2: Arm B regorafenib or TAS-102
Subjects received either regorafenib or TAS-102 based on physician and patient preference. Subjects that had received one of these standard of care drugs (regorafenib or TAS-102) prior to enrollment received the other on study.
Regorafenib taken daily from days 1-21 of each 28-day cycle or TAS-102 taken twice daily on days 1-5 and 8-12 of each 28-day cycle.
Subjects who had disease progression on Arm B were given the option to receive Arm A study drugs after a 14 day wash-out period.
干预措施: TAS-102 (Drug)
Phase 2: Arm B regorafenib or TAS-102
Subjects received either regorafenib or TAS-102 based on physician and patient preference. Subjects that had received one of these standard of care drugs (regorafenib or TAS-102) prior to enrollment received the other on study.
Regorafenib taken daily from days 1-21 of each 28-day cycle or TAS-102 taken twice daily on days 1-5 and 8-12 of each 28-day cycle.
Subjects who had disease progression on Arm B were given the option to receive Arm A study drugs after a 14 day wash-out period.
干预措施: SGI-110 (Drug)
Phase 2: Arm B regorafenib or TAS-102
Subjects received either regorafenib or TAS-102 based on physician and patient preference. Subjects that had received one of these standard of care drugs (regorafenib or TAS-102) prior to enrollment received the other on study.
Regorafenib taken daily from days 1-21 of each 28-day cycle or TAS-102 taken twice daily on days 1-5 and 8-12 of each 28-day cycle.
Subjects who had disease progression on Arm B were given the option to receive Arm A study drugs after a 14 day wash-out period.
干预措施: Irinotecan (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Up to 12 months
Progression Free Survival is the time (in months) from start of treatment to progression, clinical deterioration attributed to disease, or death.
Number of Participants Experiencing a Dose Limiting Toxicity
时间窗: 28 days
Number of participants experiencing a Dose Limiting Toxicity (DLT) in each dose level. DLT is defined as any of the following study drug-related toxicities occurring during the first cycle of study drug on study: 1. grade 4 thrombocytopenia lasting \>7days 2. any grade 3-4 febrile neutropenia 3. grade 3 or higher non-hematologic toxicity unless it could be managed by supportive treatment 4. any other clinically significant adverse event which would place subjects at undue safety risk, or results in discontinuation of treatment.
次要结局
- Overall Survival(Up to 3 years)
- Objective Response Rate(Assessed until disease progression, up to 3 years)