Phase I/II Study of SGI-110 With Irinotecan Versus Regorafenib or TAS-102 in Metastatic Colorectal Cancer
- Conditions
- Previously Treated Metastatic Colorectal Cancer
- Interventions
- Registration Number
- NCT01896856
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 118
- 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.
- 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-110.
- 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-102. 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 2: Arm A SGI-110 + irinotecan SGI-110 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. Phase 1: Dose Escalation SGI-110 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. Phase 2: Arm B regorafenib or TAS-102 SGI-110 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. Phase 2: Arm A SGI-110 + irinotecan 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. Phase 2: Arm B regorafenib or TAS-102 Regorafenib 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. Phase 2: Arm B regorafenib or TAS-102 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. Phase 2: Arm B regorafenib or TAS-102 Irinotecan 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.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) 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 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.
- Secondary Outcome Measures
Name Time Method Overall Survival Up to 3 years Overall Survival is defined as the time (in months) between the start of treatment and death.
Objective Response Rate Assessed until disease progression, up to 3 years Objective Response Rate (ORR) is defined as the number of subjects achieving a Complete Response (CR) or Partial Response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. CR = disappearance of all target lesions, PR = at least 30% decrease in the sum of diameters of target lesions.
Trial Locations
- Locations (4)
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
USC / Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
VU Medisch Centrum
🇳🇱Amsterdam, Netherlands