Phase I/II Study of SGI-110 With Irinotecan Versus Regorafenib or TAS-102 in Metastatic Colorectal Cancer
Previously Treated Metastatic Colorectal Cancer
About this trial
This is an interventional treatment trial for Previously Treated Metastatic Colorectal Cancer focused on measuring SGI-110, irinotecan, regorafenib, methylation, colorectal, metastatic, TAS-102, lonsurf
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- USC / Norris Comprehensive Cancer Center
- Sidney Kimmel Comprehensive Cancer Center
- Memorial Sloan Kettering Cancer Center
- VU Medisch Centrum
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Active Comparator
Phase 1: Dose Escalation
Phase 2: Arm A SGI-110 + irinotecan
Phase 2: Arm B regorafenib or TAS-102
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.
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.
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.