Clinical trial NCT01896856: Phase I/II Study of SGI-110 With Irinotecan Versus Regorafenib or TAS-102 in Metastatic Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Previously Treated Metastatic Colorectal Cancer
Keywords: SGI-110
irinotecan
regorafenib
methylation
colorectal
metastatic
TAS-102
lonsurf
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Van Andel Research Institute
name: Astex Pharmaceuticals, Inc.
First posted: 2013-07-11
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In Phase 2, Arm B patients who have disease progression will be given the option to receive Arm A study drugs.
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Number of Participants Experiencing a Dose Limiting Toxicity
timeFrame: 28 days
measure: Progression Free Survival (PFS)
timeFrame: Up to 12 months
Secondary outcomes:
measure: Overall Survival
timeFrame: Up to 3 years
measure: Objective Response Rate
timeFrame: Assessed until disease progression, up to 3 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
Study officials:
affiliation: SKCCC at JHMI
name: Nilo Azad, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sharma A, Vatapalli R, Abdelfatah E, Wyatt McMahon K, Kerner Z, A Guzzetta A, Singh J, Zahnow C, B Baylin S, Yerram S, Hu Y, Azad N, Ahuja N. Hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells. PLoS One. 2017 Apr 26;12(4):e0176139. doi: 10.1371/journal.pone.0176139. eCollection 2017.