A Non-randomized, Open-label, Single-center Phase Ib Study of Short Cycles of SUnitinib Alternating With REgorafenib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) Progressing After Prior Therapy With Tyrosine Kinase Inhibitors: SURE Trial

A Non-randomized, Open-label, Single-center Phase Ib Study of Short Cycles of SUnitinib Alternating With REgorafenib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) Progressing After Prior Therapy With Tyrosine Kinase Inhibitors: SURE Trial

Gastrointestinal Stromal Tumor

Ongoing, but not recruiting

1

Start Date 06/01/2014

Age of Trial (yrs) 11

Gleevec-resistant

KIT/PDGFRA/VEGF inhibitors

Specifically GIST and only GIST

14-149 SURE Trial

Dana-Farber Cancer Institute

Suzanne George, MD 617-632-5204 sgeorge2@partners.org

Oral

This is a non-randomized, open label, single-center, single-arm, phase Ib study to evaluate the safety and the preliminary efficacy of short cycles of sunitinib alternated with regorafenib in participants with metastatic and/or unresectable gastrointestinal stromal tumor GISTs with prior failure of tyrosine kinase inhibitors (TKI). The study consists of two cohorts: a dose-escalation, dose-finding cohort, and dose-expansion cohort. Between 6 to 15 patients are expected to be included in the escalation cohort. A total of 20 eligible and evaluable patients will be included in the expansion cohort to further assess toxicity and evaluate preliminary efficacy.

Each treatment cycle lasts 28 days (4 weeks), during which time you will be taking the study drug, sunitinib, for the first 3 days of the week, followed by the study drug, regorafenib, for the last 4 days of the week. The study drugs will be taken continuously for 4 weeks each cycle, unless the study team instructs you otherwise. Each participant will receive a study diary. The diary will also include special instructions for taking the study drugs.

Each treatment cycle lasts 28 days (4 weeks), during which time you will be taking the study drug, sunitinib, for the first 3 days of the week, followed by the study drug, regorafenib, for the last 4 days of the week. The study drugs will be taken continuously for 4 weeks each cycle, unless the study team instructs you otherwise. Each participant will recieve a srudy diary. The diary will also include special instructions for taking the study drugs.

Inclusion Criteria include:

Histologically confirmed metastatic and/or unresectable GIST. Patients must demonstrate prior failure to at least imatinib, sunitinib and regorafenib (4th line and beyond). Any number of previous therapies for GIST is allowed.

Failure of imatinib is defined as either prior progression of disease on imatinib in the metastatic setting or progression during adjuvant imatinib, or within 3 months of completing adjuvant imatinib. Failure of sunitinib and regorafenib is defined only as prior progression of disease on sunitinib or on regorafenib as assessed by the investigator.

Exclusion Criteria include:

Patients will be ineligible for enrollment into the study if they meet any of the following criteria. Unless specified, all patients in dose-escalation cohort and dose-expansion cohort must meet all of the following inclusion criteria to be eligible for enrollment into the study:

Patients with intolerance to sunitinib and/or regorafenib.

Clinically significant cardiac arrhythmias and/or patients who require anti-arrhythmic therapy (excluding beta blockers or digoxin). Patients with controlled atrial fibrillation are not exluded.

History of clinically significant cardiac disease or congestive heart failure > NYHA class 2 (See Appendix C). Patients must not have unstable angina (anginal symptoms at rest) or new-onset angina within the last 3 months or myocardial infarction within the past 6 months.

Hypertension as defined by systolic blood pressure >140 mmHg or diastolic blood pressure > 90 mmH despite optimal medical management.

Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication (except for adequately treated catheter-related venous thrombosis occurring more than 1 month before the start of study medication).

Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.