Phase I/II Study of SGI-110 With Irinotecan Versus Regorafenib or TAS-102 in Metastatic Colorectal Cancer

Johns Hopkins Medicine

Status and phase: Completed; Phase 2; Phase 1

Conditions: Previously Treated Metastatic Colorectal Cancer

Treatments: Drug: SGI-110; Drug: Irinotecan; Drug: TAS-102; Drug: SGI-110 Dose Escalation; Drug: Regorafenib

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01896856

NA_00085870 (Other Identifier)

J1369

Details and patient eligibility

About

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).

Enrollment: 118 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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118 participants in 3 patient groups

Phase 1: Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: SGI-110 Dose Escalation

Phase 2: Arm A SGI-110 + irinotecan

Experimental group

Description:

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.

Treatment:

Drug: Irinotecan

Drug: SGI-110

Phase 2: Arm B regorafenib or TAS-102

Active Comparator group

Description:

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.

Treatment:

Drug: Irinotecan

Drug: TAS-102

Drug: Regorafenib

Drug: SGI-110