Phase 3 Study of DCC-2618 vs Placebo in Advanced GIST Patients Who Have Been Treated With Prior Anticancer Therapies

Not Recruiting

Trial ID: NCT03353753


This is a 2-arm, randomized, placebo-controlled, double-blind, international, multicenter study comparing the efficacy of ripretinib (DCC-2618) to placebo in patients who have received treatment with prior anticancer therapies. Prior anticancer therapies must include imatinib, sunitinib, and regorafenib (3 prior therapies). Approximately 120 patients were randomized in a 2:1 ratio to ripretinib 150 mg QD or placebo

Official Title

A Phase 3, INterVentional, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of DCC-2618 In Patients With AdvanCed Gastrointestinal Stromal TUmorS Who Have Received Treatment With Prior Anticancer Therapies

Stanford Investigator(s)

Kristen N Ganjoo
Kristen N Ganjoo

Professor of Medicine (Oncology)


Inclusion Criteria:

   1. Histologic diagnosis of GIST

   2. Patients must have progressed on imatinib, sunitinib, and regorafenib or have
   documented intolerance to any of these treatments.

   3. ECOG PS of 0 to 2 at screening.

   4. Able to provide an archival tumor tissue sample if no anticancer therapy was
   administered since the sample was collected; otherwise, a fresh tumor tissue sample is
   required prior to the first dose of study drug.

   5. Female patients of childbearing potential must have a negative serum beta-human
   chorionic gonadotrophin (β-hCG) pregnancy test at screening and negative urine
   pregnancy test at Cycle 1 Day 1 prior to the first dose of study drug.

   6. Patients of reproductive potential must agree to follow the contraception

   7. The patient is capable of understanding and complying with the protocol and has signed
   the informed consent document. A signed informed consent form must be obtained before
   any study-specific procedures are performed.

   8. At least 1 measurable lesion according to modified RECIST Version 1.1 (non-nodal
   lesions must be ≥1.0 cm in the long axis or ≥double the slide 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 following
   laboratory assessments performed at screening.

      - Absolute neutrophil count ≥1000/uL

      - Hemoglobin ≥8 g/dL

      - Platelet count ≥75,000/uL

      - Total bilirubin ≤1.5 x the upper limit of normal (ULN)

      - Aspartate transaminase or alanine transaminase ≤3 x ULN (≤5x ULN in the presence
      of hepatic metastases)

      - Serum creatinine ≤1.5 x ULN or creatinine clearance ≥50 mL/min based on either
      urine collection or Cockcroft Gault estimation.

      - Prothrombin time (PT) or international normalized ratio (INR) or partial
      thromboplastin time ≤1.5 x ULN. Patients on a stable, maintenance regimen of
      anticoagulant therapy for at least 30 days prior to study drug administration may
      have PT/INR measurements >1.5 x ULN if, in the opinion of the Investigator, the
      patient is suitable for the study. An adequate rationale must be provided to the
      Sponsor prior to randomization.

10. Resolution of all toxicities from prior therapy to ≤Grade 1 (or baseline) within 1
   week prior to the first dose of study drug (excluding alopecia and ≤Grade 3 clinically
   asymptomatic lipase, amylase, and creatine phosphokinase laboratory abnormalities).

Exclusion Criteria:

   1. Treatment with anticancer therapy, including investigational therapy, or
   investigational procedures within 14 days or 5 x the half-life (whichever is longer)
   prior to the first dose of study drug. For prior biological therapies, eg, monoclonal
   antibodies with a half-life longer than 3 days, the interval must be at least 28 days
   prior to the first dose of study drug.

   2. Prior treatment with DCC-2618

   3. Prior or concurrent malignancy whose natural history or treatment have the potential
   to interfere with the safety or efficacy assessment of DCC-2618. Patients receiving
   adjuvant cancer treatment are not eligible if those medications are potentially active
   against GIST or excluded per protocol.

   4. Patient has known active central nervous system metastases.

   5. New York Heart Association class II - IV heart disease, active ischemia or any other
   uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac
   arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure.

   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 (eg, deep vein thrombosis) or pulmonary arterial events (eg,
   pulmonary embolism) within 3 months before the first dose of study drug. Patients with
   venous thrombotic events ≥3 months before the first dose of study drug on stable
   anticoagulation therapy are eligible.

   8. 12-lead electrocardiogram (ECG) demonstrating QT interval corrected by Fridericia's
   formula >450 ms in males or >470 ms in females at screening or history of long QT
   interval corrected syndrome.

   9. Left ventricular ejection fraction (LVEF) <50% at screening.

10. Use of proton-pump inhibitors within 4 days prior to the first dose of study drug.
   Other medications that increase gastric pH, ie, histamine H2 receptor antagonists and
   antacids may be taken provided they are not administered within 2 hours before or
   after administration of study drug.

11. Use of strong or moderate inhibitors and inducers of cytochrome P450 (CYP) 3A4,
   including certain herbal medications (eg, St. John's Wort) and consumption of
   grapefruit or grapefruit juice within 14 days or 5 x the half-life (whichever is
   longer) prior to the first dose of study drug.

12. Use of known substrates or inhibitors of breast cancer resistance protein (BCRP)
   transporters within 14 days or 5 x the half-life (whichever is longer) prior to the
   first dose of study drug.

13. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study
   drug. Following major surgeries, >4 weeks prior to the first dose of study drug, all
   surgical wounds must be healed and free of infection or dehiscence.

14. Any other clinically significant comorbidities, such as uncontrolled pulmonary
   disease, active infection, or any other condition, which in the judgment of the
   Investigator, could compromise compliance with the protocol, interfere with
   interpretation of the study results, or predispose the patient to safety risks.

15. 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.

16. If female, the patient is pregnant or lactating.

17. Known allergy or hypersensitivity to any component of the investigational drug
   product. Patients with a history of Stevens-Johnson syndrome on a prior TKI are

18. Gastrointestinal abnormalities including but not limited to:

      - inability to take oral medication

      - malabsorption syndromes

      - requirement for intravenous alimentation

19. Any active bleeding excluding hemorrhoidal or gum bleeding.


drug: DCC-2618

drug: Placebo Oral Tablet

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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