Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting
Trial record 2 of 23 for:    tas-102

Phase I Study of SGI-110 With Irinotecan Followed by Randomized Phase II Study of SGI-110 With Irinotecan Versus Regorafenib or TAS-102 in Previously Treated Metastatic Colorectal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Sidney Kimmel Comprehensive Cancer Center
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center Identifier:
First received: July 8, 2013
Last updated: September 13, 2016
Last verified: September 2016
This is a phase I/randomized phase II study of the combination of 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 TAS-102.

Condition Intervention Phase
Previously Treated Metastatic Colorectal Cancer
Drug: SGI-110
Drug: Irinotecan
Drug: regorafenib
Drug: TAS-102
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Phase 1/2: SGI-110 + irinotecan versus regorafenib or TAS-102 adverse events [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    In Phase 1, subjects will be assessed for adverse events attributable to SGI-110 and/or irinotecan. In Phase 2, subjects will be assessed for adverse events attributable to SGI-110 and/or irinotecan versus regorafenib or TAS-102.

  • Phase 1/2: Response [ Time Frame: 4 ] [ Designated as safety issue: No ]
    Subjects will be monitored for response via RECIST 1.1 criteria.

Secondary Outcome Measures:
  • Phase 1/2: survival [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Subjects will be monitored for survival (overall survival versus progression free survival).

Estimated Enrollment: 108
Study Start Date: September 2013
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Phase 1/2: SGI-110 + irinotecan
The SGI-110 + irinotecan arm will be used in both the phase 1 and phase 2 parts of the study. In phase 1, the maximum tolerated dose will be determined.
Drug: SGI-110 Drug: Irinotecan
Active Comparator: Phase 2: regorafenib
In phase 2, we will compare SGI-110 + irinotecan to regorafenib or TAS-102.
Drug: regorafenib
Active Comparator: Phase 2: TAS-102
In phase 2, we will compare SGI-110 + irinotecan to regorafenib or TAS-102
Drug: TAS-102
Other Name: lonsurf


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Participants must have histologically or cytologically confirmed adenocarcinoma of the colon or rectum
  • Patients in the phase II cohort must be amenable to having two research biopsies. This applies to the first 36 patients enrolled to Arm A, who have both biopsiable disease and are randomized to SGI-110 + Irinotecan.
  • Archival tissue must be procured if available
  • Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan. See section 10 for the evaluation of measureable disease.
  • Patients in the phase II cohort must have progressed while receiving irinotecan therapy in the metastatic setting. There are no limitations on number of prior therapies in the metastatic setting.
  • Age minimum of 18 years.
  • Life expectancy of greater than 12 weeks.
  • ECOG performance status <1
  • Participants must have normal organ and marrow function
  • The effects of SGI-110 on the developing human fetus are unknown. For this reason and because oncological agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 3 months after completion of the study.

Should a woman become pregnant or suspect she is pregnant while participating in this study or within 30 days of last dose, she should inform her treating physician immediately.

  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to enrolling in the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  • Participants may not be receiving any other study agents.
  • Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to irinotecan, decitabine or SGI-110.
  • Subjects who have 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 women are excluded from this study because SGI-110 is a/an hypomethylating agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with SGI-110, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study.
  • Individuals with a history of a different malignancy are ineligible except for the following circumstances: Individuals with a history of other malignancies who have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, definitively treated early stage prostate cancer (confined to prostate with Gleason 6 or below), definitely 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 are ineligible because of the potential for pharmacokinetic interactions with SGI-110. In addition, as these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
  • Previous treatment with regorafenib and TAS-102 (This applies to phase II only.) If patients have previously received either regorafenib OR TAS-102, they must be able to receive the alternate regimen if randomized to the standard of care arm).
  • Hospitalization for an acute medical issue within 4 weeks prior to screening visit that would not otherwise be managed in an infusion center or outpatient clinic setting (e.g., a patient admitted to complete a transfusion would not be ineligible.).
  • Symptomatic bowel obstruction within 6 months prior to enrollment, Patients who undergo surgical correction of obstructing lesion will be eligible within 6 months.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01896856

Contact: Ellen Lilly-Foreman, RN 443-287-4961
Contact: Thomas Brown 410-502-5328

United States, California
USC / Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Anthony El-Khoueiry, MD    323-865-3967   
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Thomas S Brown, MSCIS    410-502-5328   
Principal Investigator: Nilo Azad, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Derek Alexander    646-888-1381   
Principal Investigator: Andrea Cercek, MD         
VU Medisch Centrum Recruiting
Amsterdam, Netherlands, 1081 HV
Contact: Henk Verheul, MD   
Contact: Elske Gootjes, MD   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Principal Investigator: Nilo Azad, MD SKCCC at JHMI
  More Information

Responsible Party: Sidney Kimmel Comprehensive Cancer Center Identifier: NCT01896856     History of Changes
Other Study ID Numbers: J1369  NA_00085870 
Study First Received: July 8, 2013
Last Updated: September 13, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic processed this record on October 21, 2016