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.

Completed

Conditions: Gemetastaseerd colorectaal carcinoom
metastatic colorectal cancer
10017990

Registration Number: NL-OMON47325

Lead Sponsor: Vrije Universiteit Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 28

Inclusion Criteria

Histologically or cytologicaly confirmed adenocarcinoma of the colon or rectum,
Patients in phase I must have biopsiable diasese and be amenable to having two research biopsies.
Patients must have progressed on irinotecan therapy in the metastic setting. There are no limitation on number of prior therapies. They should have a life expectancy of greater than 12 weeks, an
ECOG of

Exclusion Criteria

Chemotherapy or radiotherapy within 4 weeks prior to entering the study,
Known brain metastases,
Uncontrolled intercurrent illness,
Prior therapy with any hypomethylating agent,
Pregnancy
A history of a different malignancy unless disease-free for at least 5 years,
HIV positive individuals on HAART
Previoius treatement with regorafenb and TAS-102 (this applies to phase II only. If patients have previously received aeither 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
Symptomatic bowel obstruction within 6 months prior to enrollment. Patients who undergo surgical correction of obstructing lesion will be eligible within 6 months.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>During phase I, we will be assessing the safety and tolerability of SGI-110 in<br /><br>combination with irinotecan, as well as determine the dose of SGI-110 that will<br /><br>be used in combination with irinotecan during the phase II portion of this<br /><br>trial.<br /><br>Phase II: To improve median progression-free survival from that reported with<br /><br>regorafenib and TAS-102 to 4 months for SGI-110+irinotecan in previously<br /><br>treated metastatic colon cancer patients who have progressed on irinotecan.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>In Fase I we will also be assessing the changes in global methylation and<br /><br>expression at the tumor level with SGI-110 and irinotecan treatment and the<br /><br>pharmacokinetic interactions of SGI-110 and irinotecan.<br /><br>In phase II we will also evaluate the following: response rate as determined by<br /><br>RECIST criteria 1.1, evaluate concurrent SGI-110 and irinotecan treatment<br /><br>versus regorafenib alone, assess whether SGI-110 in combination with irinotecan<br /><br>can improve median overall survival from the historical rate of 6.4 months, and<br /><br>assess for potential predictive biomarkers of response and survival using<br /><br>baseline tissue.</p><br>