Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This is a 2-arm, randomized, open-label, international, multicenter study comparing the
efficacy of DCC-2618 to sunitinib in GIST patients who progressed on or were intolerant to
first-line anticancer treatment with imatinib. Approximately 426 patients will be randomized
in a 1:1 ratio to DCC-2618 150 mg once daily (QD) (continuous dosing for 6 week cycles) or
sunitinib 50 mg QD (6 week cycles, 4 weeks on, 2 weeks off).
Phase
Phase 3
Funding Agency/Sponsor
Industrial
Disease
Bone and Soft Tissue Cancers
Enrollment Eligibility
Inclusion Criteria:
1. Patients ≥ 18 years of age at the time of informed consent.
2. Histologic diagnosis of GIST and must be able to provide an archival tumor tissue
sample, otherwise, a fresh biopsy is required.
3. Molecular pathology report must be available. If molecular pathology report is not
available or insufficient, an archival tumor tissue sample or fresh biopsy is required
for mutation status confirmation by the central laboratory prior to randomization.
4. Patients must have progressed on imatinib or have documented intolerance to imatinib.
5. Eastern Cooperative Oncology Group (ECOG) PS of ≤ 2 at screening.
6. Female patients of childbearing potential must have a negative serum beta-human
chorionic gonadotropin (β-hCG) pregnancy test at screening and negative pregnancy test
at Cycle 1 Day 1 prior to the first dose of study drug.
7. Patients of reproductive potential must agree to follow the contraception requirements
outlined in the study protocol.
8. Patients must have at least 1 measurable lesion according to mRECIST Version 1.1 (non
nodal lesions must be ≥ 1.0 cm in the long axis or ≥ double the slice thickness in the
long axis) within 21 days prior to the first dose of study drug.
9. Adequate organ function and bone marrow reserve as indicated by the central laboratory
assessments performed at screening.
10. Resolution of all toxicities from prior therapy to ≤ Grade 1 (or patient baseline)
within 1 week prior to the first dose of study drug (excluding alopecia and ≤ Grade 3
clinically asymptomatic lipase, amylase, and creatine phosphokinase [CPK] laboratory
abnormalities).
11. The patient is capable of understanding and complying with the protocol and the
patient has signed the informed consent document. Signed informed consent form (ICF)
must be obtained before any study-specific procedures are performed and the patient
must agree to not participate in any other interventional clinical trial while on
treatment in this clinical trial. Participation in a noninterventional study
(including observational studies) is permitted.
Exclusion Criteria:
1. Treatment with any other line of therapy in addition to imatinib for advanced GIST.
Imatinib-containing combination therapy in the first-line setting is not allowed.
2. Patients with a prior or concurrent malignancy whose natural history or treatment have
the potential to interfere with the safety or efficacy assessment of this clinical
trial are not eligible.
3. Patient has known active central nervous system metastases.
4. New York Heart Association class II-IV heart disease, myocardial infarction within 6
months of cycle 1 day 1, active ischemia or any other uncontrolled cardiac condition
such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy,
uncontrolled hypertension or congestive heart failure.
5. Left ventricular ejection fraction (LVEF) < 50% at screening.
6. Arterial thrombotic or embolic events such as cerebrovascular accident (including
ischemic attacks) or hemoptysis within 6 months before the first dose of study drug.
7. Venous thrombotic events (e.g. deep vein thrombosis) or pulmonary arterial events
(e.g. pulmonary embolism) within 1 month before the first dose of study drug. Patients
on stable anticoagulation therapy for at least one month are eligible.
8. 12-lead ECG demonstrating QT interval corrected (QTc) by Fridericia's formula > 450 ms
in males or > 470 ms in females at screening or history of long QTc syndrome
9. Use of known substrates or inhibitors of BCRP transporters within 14 days or 5 x the
half-life (whichever is longer) prior to the first dose of study drug.
10. Major surgeries (e.g. abdominal laparotomy) within 4 weeks of the first dose of study
drug. All major surgical wounds must be healed and free of infection or dehiscence
before the first dose of study drug.
11. Any other clinically significant comorbidities.
12. Known human immunodeficiency virus or hepatitis C infection only if the patient is
taking medications that are excluded per protocol, active hepatitis B, or active
hepatitis C infection.
13. If female, the patient is pregnant or lactating.
14. Known allergy or hypersensitivity to any component of the study drug.
15. Gastrointestinal abnormalities including but not limited to:
- inability to take oral medication
- malabsorption syndromes
- requirement for intravenous (IV) alimentation
16. Any active bleeding excluding hemorrhoidal or gum bleeding.