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

NCT03353753 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: DCC-2618-03-001
• Study Type: interventional
• Target: 129
• Locations: 13 countries
• Sites: 35

Brief Summary

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

Conditions

Gastrointestinal Stromal Tumors

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS was defined as the time interval between the date of randomization and the earliest documented evidence of the first disease progression based on the independent radiologic review or death due to any cause on initially assigned study treatment, whichever comes earlier, assessed at 26, 39, and 52 weeks.

  From date of randomization to the earliest date of disease progression or death from any cause [through database cutoff 31-May-2019 (up to approximately 15 months)].

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  From date of randomization to the earliest date of disease progression or death from any cause [through database cutoff 31-May-2019 (up to approximately 15 months)].

• Time to Tumor Progression (TTP) Based on Independent Radiologic Review

  From date of randomization to the earliest date of disease progression [through database cutoff 31-May-2019 (up to approximately 15 months)].

• Overall Survival (OS)

  From the date of randomization to the date of death from any cause [through database cutoff 31-May-2019 (up to approximately 15 months)].

• Quality of Life & Disease-Related Symptoms - European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer 30-Item - Role Functioning

  From the date of randomization (Baseline) to Cycle 2 Day 1 (Month 2)

• Quality of Life & Disease-Related Symptoms - Physical Functioning

  From the date of randomization (Baseline) to Cycle 2 Day 1 (Month 2)

Study Arms (2)

Arm 1

ACTIVE COMPARATOR

150 mg QD DCC-2618

Drug: DCC-2618

Arm 2

PLACEBO COMPARATOR

Placebo

Drug: Placebo Oral Tablet

Interventions

DCC-2618 DRUG

Oral KIT/PDGFRA kinase inhibitor

Also known as: ripretinib

Arm 1

Placebo Oral Tablet DRUG

Placebo

Arm 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic diagnosis of GIST
• Patients must have progressed on imatinib, sunitinib, and regorafenib or have documented intolerance to any of these treatments.
• ECOG PS of 0 to 2 at screening.
• 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.
• 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.
• Patients of reproductive potential must agree to follow the contraception requirements.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• Prior treatment with DCC-2618
• 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.
• Patient has known active central nervous system metastases.
• 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.
• 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 (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.
• 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.
• Left ventricular ejection fraction (LVEF) \<50% at screening.
• 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.
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Deciphera Pharmaceuticals, LLC: lead

Study Sites (35)

HonorHealth

Scottsdale, Arizona, 85260, United States

Location

University of Southern California - Norris

Los Angeles, California, 90033, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

Stanford

Stanford, California, 94305, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Georgia Cancer Specialists

Atlanta, Georgia, 30341, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Columbia

New York, New York, 10027, United States

Location

MSKCC

New York, New York, 10065, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Alfred University

Melbourne, Australia

Location

University Hospital Leuven

Leuven, Belgium

Location

Cross Cancer Center

Edmonton, Alberta, Canada

Location

Princess Margaret Hospital

Toronto, Canada

Location

Helsinki University Central Hospital

Helsinki, Finland

Location

Institut Bergonié

Bordeaux, France

Location

Le Centre Léon Bérard

Lyon, France

Location

Gustave-Roussy

Villejuif, France

Location

Sarcoma Center Brandenburg

Brandenburg, Germany

Location

University Hospital Essen

Essen, Germany

Location

Universitätsmedizin Mannheim

Mannheim, Germany

Location

Istituto Nazionale dei Tumori

Milan, Italy

Location

Università Campus Bio-Medico di Roma

Rome, Italy

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Maria Sklodowska-Curie Memorial Cancer Center

Warsaw, Poland

Location

NCC

Singapore, 169610, Singapore

Location

Vall d'Hebron

Barcelona, Spain

Location

Hospitalario Universitario Virgen del Rocío

Seville, Spain

Location

Royal Marsden

London, United Kingdom

Location

University of Sheffield

Sheffield, United Kingdom

Location

Related Publications (3)

• Schoffski P, George S, Heinrich MC, Zalcberg JR, Bauer S, Gelderblom H, Serrano C, Jones RL, Attia S, D'Amato G, Chi P, Reichardt P, Becker C, Shi K, Meade J, Ruiz-Soto R, Blay JY, von Mehren M. Patient-reported outcomes in individuals with advanced gastrointestinal stromal tumor treated with ripretinib in the fourth-line setting: analysis from the phase 3 INVICTUS trial. BMC Cancer. 2022 Dec 13;22(1):1302. doi: 10.1186/s12885-022-10379-9.

  PMID: 36514034 DERIVED

• Symcox M, Somaiah N. Ripretinib for advanced gastrointestinal stromal tumor: Plain language summary of the INVICTUS study. Future Oncol. 2021 Dec 1;17(36):5007-5012. doi: 10.2217/fon-2021-0803. Epub 2021 Oct 18.

  PMID: 34661454 DERIVED

• Blay JY, Serrano C, Heinrich MC, Zalcberg J, Bauer S, Gelderblom H, Schoffski P, Jones RL, Attia S, D'Amato G, Chi P, Reichardt P, Meade J, Shi K, Ruiz-Soto R, George S, von Mehren M. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Jul;21(7):923-934. doi: 10.1016/S1470-2045(20)30168-6. Epub 2020 Jun 5.

  PMID: 32511981 DERIVED

Related Links

• Deciphera Company Website

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

ripretinib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Results Point of Contact

• Title: INVICTUS Clinical Team
• Organization: Deciphera Pharmaceuticals, LLC

clinicaltrials@deciphera.com

7812096400

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2017
• First Posted: November 27, 2017
• Study Start: February 27, 2018
• Primary Completion: May 31, 2019
• Study Completion: May 11, 2022
• Last Updated: November 21, 2022
• Results First Posted: April 23, 2021

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (15); FR (3); NL (1); AU (1); SG (1); CA (2); BE (1); FI (1); IT (2); ES (2); DE (3); GB (2); PL (1)