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

Previously Treated Metastatic Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01896856
• Other study ID #: J1369
• Secondary ID: NA_00085870
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 23, 2013
• Est. completion date: August 26, 2019

Study information

• Verified date: August 2020
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: August 26, 2019
• Est. primary completion date: August 26, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Previously Treated Metastatic Colorectal Cancer

Intervention

Drug:
• SGI-110 Dose Escalation
Dose level 1 (DL1): 45 mg/m^2 administered as a subcutaneous injection Dose level 1G (DL1G): 45 mg/m^2 administered as a subcutaneous injection + growth factor support Dose level -1 (DL-1): 30 mg/m^2 administered as a subcutaneous injection Dose level -1G (DL-1G): 30 mg/m^2 administered as a subcutaneous injection + growth factor support
• Regorafenib
160 mg taken orally
• TAS-102
35 mg/m^2 taken orally
• SGI-110
45 mg/m^2 administered as a subcutaneous injection
• Irinotecan
125 mg/m^2 administered IV

Locations

Country	Name	City	State
Netherlands	VU Medisch Centrum	Amsterdam
United States	Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Astex Pharmaceuticals, Inc., Van Andel Research Institute

Countries where clinical trial is conducted

United States,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Experiencing a Dose Limiting Toxicity	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: grade 4 thrombocytopenia lasting >7days; any grade 3-4 febrile neutropenia; grade 3 or higher non-hematologic toxicity unless it could be managed by supportive treatment; any other clinically significant adverse event which would place subjects at undue safety risk, or results in discontinuation of treatment.	28 days
Primary	Progression Free Survival (PFS)	Progression Free Survival is the time (in months) from start of treatment to progression, clinical deterioration attributed to disease, or death.	Up to 12 months
Secondary	Overall Survival	Overall Survival is defined as the time (in months) between the start of treatment and death.	Up to 3 years
Secondary	Objective Response Rate	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.	Assessed until disease progression, up to 3 years