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

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ClinicalTrials.gov Identifier: NCT03353753
Recruitment Status : Recruiting
First Posted : November 27, 2017
Last Update Posted : October 8, 2018
Sponsor:
Information provided by (Responsible Party):
Deciphera Pharmaceuticals LLC

Brief Summary:
This is a 2‑arm, randomized, placebo-controlled, double‑blind, international, multicenter study comparing the efficacy of 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 will be randomized in a 2:1 ratio to DCC‑2618 150 mg QD or placebo

Condition or disease Intervention/treatment Phase
Gastrointestinal Stromal Tumors Drug: DCC-2618 Drug: Placebo Oral Tablet Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : February 27, 2018
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Active Comparator: Arm 1
150 mg QD DCC-2618
Drug: DCC-2618
Oral KIT/PDGFRA kinase inhibitor

Placebo Comparator: Arm 2
Placebo
Drug: Placebo Oral Tablet
Placebo




Primary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: 15 months ]
    PFS Based on independent radiologic review using modified RECIST


Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 15 months ]
    Objective response rate as determined by confirmed CR + confirmed PR by independent radiologic review

  2. Time to Tumor Progression (TTP) based on independent radiologic review [ Time Frame: 15 months ]
    TTP based on independent radiologic review

  3. Overall Survival (OS) [ Time Frame: 15 months ]
  4. Time to best response [ Time Frame: 15 months ]
    Time to best response, as defined by the independent radiologic review,

  5. Progression Free Survival (PFS) [ Time Frame: 15 months ]
    PFS based on investigator assessment

  6. Quality of Life [ Time Frame: 18 months ]
    Changes from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer 30‑item and EuroQol 5-Dimension 5-Level

  7. Disease control rate (DCR) [ Time Frame: 12 weeks ]
    DCR as determined by complete response [CR] + partial response [PR] + stable disease



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 requirements.
  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. Has a known additional malignancy that is progressing or required active treatment within 3 years of the first dose of study drug. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or other in situ cancers.
  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.
  18. Gastrointestinal abnormalities including but not limited to:

    • inability to take oral medication
    • malabsorption syndromes
    • requirement for intravenous alimentation active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia, or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03353753


Contacts
Contact: Clinical Team INVICTUS 781.209.6400 clinicaltrials@deciphera.com

  Show 36 Study Locations
Sponsors and Collaborators
Deciphera Pharmaceuticals LLC

Additional Information:
Responsible Party: Deciphera Pharmaceuticals LLC
ClinicalTrials.gov Identifier: NCT03353753     History of Changes
Other Study ID Numbers: DCC-2618-03-001
First Posted: November 27, 2017    Key Record Dates
Last Update Posted: October 8, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases