A Study of DCC-2618 vs. Sunitinib in Advanced GIST Patients after Treatment with Imatinib

Overview

  • Study type

    Interventional
  • Study phase

    III
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 18-009703
    • Scottsdale/Phoenix, Arizona: 18-009703
    • Jacksonville, Florida: 18-009703
    NCT ID: NCT03673501
    Sponsor Protocol Number: DCC-2618-03-002

About this study

The purpose of this study is to compare the effectiveness of DCC-2618 to sunitinib in GIST patients who progressed on or were intolerant to first-line anticancer treatment with imatinib. Approximately 358 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).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

 

  • Patients ≥ 18 years of age at the time of informed consent.
  • Histologic diagnosis of GIST and must be able to provide an archival tumor tissue sample, otherwise, a fresh biopsy is required.
  • Molecular pathology report with mutational status of KIT/PDGFRA must be available. Mutation status must be identified using a PCR or sequencing based assay. Molecular pathology report with mutation status of KIT/PDGFRA must be provided to the Sponsor for review prior to randomization. If the 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.
  • Patients must have progressed on imatinib or have documented intolerance to imatinib. Imatinib treatment must have been discontinued 10 days prior to the first dose of study drug. All prior imatinib treatment will count as one line of therapy (e.g., adjuvant imatinib and dose escalation of imatinib).
  • Eastern Cooperative Oncology Group (ECOG) PS of ≤ 2 at screening.
  • Female patients of childbearing potential must have a negative serum beta-human chorionic gonadotrophin (β-hCG) pregnancy test at screening and negative pregnancy test at Cycle 1 Day 1 prior to the first dose of study drug.
  • Patients of reproductive potential must agree to follow contraception requirements outlined in Section 6.11.9.
  • 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 slide thickness in the long axis) within 21 days prior to the first dose of study drug.
  • Adequate organ function and bone marrow reserve as indicated by the following central laboratory assessments performed at screening:
    • Absolute Neutrophil Count (ANC) ≥1000/μ;
    • Hemoglobin ≥ 8 g/dL;
    • Platelet count ≥ 75,000/μ;
    • Total bilirubin ≤ 1.5 x the upper limit of normal (ULN);
    • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN (≤ 5x ULN in the presence of hepatic metastases);
    • Creatinine clearance ≥50 ml/min based on Cockcroft Gault estimation;
    • Prothrombin time (PT), international normalized ratio (INR) and partial thromboplastin time (PTT) ≤1.5 x ULN. Patients on a stable regimen of anticoagulant therapy for at least one month prior to the first dose of study drug 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.
  • 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).
  • The patient is capable of understanding and complying with the protocol and has signed the informed consent document. Signed informed consent form (ICF) must be obtained before any study-specific procedures are performed.

 Exclusion Criteria:

  • Treatment with any other line of therapy in addition to imatinib for advanced GIST.
  • 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. For example, patients receiving adjuvant cancer treatment are not eligible if those medications are potentially active against GIST or excluded per protocol.
    • NOTE: Patients with a history of breast cancer, requiring continued hormonal treatment (e.g. anti-estrogen or an aromatase inhibitor) may continue treatment. Patients with a history of prostate cancer, requiring continued support with luteinizing hormone-releasing hormone (LHRH) agonists, with or without androgens, may continue treatment.
  • Patient has known active central nervous system metastases.
  • 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.
  • Left ventricular ejection fraction (LVEF) < 50% at screening.
  • Arterial thrombotic or embolic events such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months before the first dose of study drug.
  • 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.
  • 12-lead electrocardiogram (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.
  • Use of strong or moderate inhibitors or inducers of cytochrome P450 (CYP) 3A4, including certain herbal medications (e.g., St. John’s Wort) within 14 days or 5 x the half-life (whichever is longer) prior to the first dose of study drug, and consumption of grapefruit or grapefruit juice within 14 days prior to the first dose of study drug. Please refer to the Indiana University Department of Medicine website (http://medicine.iupui.edu/clinpharm/ddis/main-table/) for guidance on medications that inhibit/induce CYP3A4 enzymes.
  • 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. Please refer to the US Food and Drug Administration’s (FDA) website for inhibitors and substrates (https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm).
  • 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.
  • 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.
  • 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.
  • If female, the patient is pregnant or lactating.
  • Known allergy or hypersensitivity to any component of the study drug. Patients with history of Stevens-Johnson syndrome on a prior tyrosine kinase inhibitor (TKI) are excluded.
  • Gastrointestinal abnormalities including, but not limited to:
    • inability to take oral medication;
    • malabsorption syndromes;
    • requirement for intravenous (IV) alimentation.
  • Any active bleeding excluding hemorrhoidal or gum bleeding.

 

 

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Steven Attia, D.O.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Steven Attia, D.O.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Steven Attia, D.O.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available

Study Results Summary

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Supplemental Study Information

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Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions