- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03353753
Phase 3 Study of DCC-2618 vs Placebo in Advanced GIST Patients Who Have Been Treated With Prior Anticancer Therapies (INVICTUS)
November 17, 2022 updated by: Deciphera Pharmaceuticals LLC
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
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
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
129
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Melbourne, Australia
- Alfred University
-
-
-
-
-
Leuven, Belgium
- University Hospital Leuven
-
-
-
-
-
Toronto, Canada
- Princess Margaret Hospital
-
-
Alberta
-
Edmonton, Alberta, Canada
- Cross Cancer Center
-
-
-
-
-
Helsinki, Finland
- Helsinki University Central Hospital
-
-
-
-
-
Bordeaux, France
- Institut Bergonie
-
Lyon, France
- Le Centre Léon Bérard
-
Villejuif, France
- Gustave-Roussy
-
-
-
-
-
Brandenburg, Germany
- Sarcoma Center Brandenburg
-
Essen, Germany
- University Hospital Essen
-
Mannheim, Germany
- Universitätsmedizin Mannheim
-
-
-
-
-
Milan, Italy
- Istituto Nazionale dei Tumori
-
Rome, Italy
- Università Campus Bio-Medico di Roma
-
-
-
-
-
Leiden, Netherlands
- Leiden University Medical Center
-
-
-
-
-
Warsaw, Poland
- Maria Sklodowska-Curie Memorial Cancer Center
-
-
-
-
-
Singapore, Singapore, 169610
- NCC
-
-
-
-
-
Barcelona, Spain
- Vall d'Hebron
-
Seville, Spain
- Hospitalario Universitario Virgen del Rocío
-
-
-
-
-
London, United Kingdom
- Royal Marsden
-
Sheffield, United Kingdom
- University of Sheffield
-
-
-
-
Arizona
-
Scottsdale, Arizona, United States, 85260
- HonorHealth
-
-
California
-
Los Angeles, California, United States, 90095
- UCLA
-
Los Angeles, California, United States, 90033
- University of Southern California - Norris
-
Stanford, California, United States, 94305
- Stanford
-
-
Florida
-
Jacksonville, Florida, United States, 32224
- Mayo Clinic - Jacksonville
-
-
Georgia
-
Atlanta, Georgia, United States, 30341
- Georgia Cancer Specialists
-
-
Illinois
-
Chicago, Illinois, United States, 60637
- University Of Chicago
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Dana Farber Cancer Institute
-
-
Minnesota
-
Minneapolis, Minnesota, United States, 55455
- University of Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic
-
-
New York
-
New York, New York, United States, 10065
- MSKCC
-
New York, New York, United States, 10027
- Columbia
-
-
Oregon
-
Portland, Oregon, United States, 97239
- Oregon Health & Science University
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19111
- Fox Chase Cancer Center
-
-
Texas
-
Houston, Texas, United States, 77030
- MD Anderson Cancer Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
- 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.
- 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:
- 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.
- 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.
- 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.
- If female, the patient is pregnant or lactating.
- 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 excluded.
Gastrointestinal abnormalities including but not limited to:
- inability to take oral medication
- malabsorption syndromes
- requirement for intravenous alimentation
- Any active bleeding excluding hemorrhoidal or gum bleeding.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Arm 1
150 mg QD DCC-2618
|
Oral KIT/PDGFRA kinase inhibitor
Other Names:
|
PLACEBO_COMPARATOR: Arm 2
Placebo
|
Placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-Free Survival (PFS)
Time Frame: 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)].
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR)
Time Frame: 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)].
|
The percentage of patients with a confirmed complete response or PR (CR: Disappearance of all target lesions and non-target lesions (if present at baseline); all lymph nodes must be non-pathological in size) or partial response (PR: >=30% decrease in the Sum of Diameters of target lesions and non-target lesions non-PD or NE or none at baseline; or target lesions CR and non-target lesions non-CR/Non-PD or NE) based on the independent radiologic review and during the initially assigned study treatment.
To be assigned a status of a CR or PR, changes in tumor measurements must be confirmed by repeat CT or MRI assessments that must be performed at least 4 weeks after the criteria for response are first met.
|
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
Time Frame: From date of randomization to the earliest date of disease progression [through database cutoff 31-May-2019 (up to approximately 15 months)].
|
TTP is defined as the interval between the date of randomization and the earliest documented evidence of disease progression based on the 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)
Time Frame: From the date of randomization to the date of death from any cause [through database cutoff 31-May-2019 (up to approximately 15 months)].
|
Overall Survival (OS) was defined as the interval between the date of randomization until the date of death or the date of last follow-up.
|
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
Time Frame: From the date of randomization (Baseline) to Cycle 2 Day 1 (Month 2)
|
Changes from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer 30-item - Role Functioning.
For the ripretinib arm the minimum and maximum for the outcome were -67 to 67; the placebo arm had a range of -83 to 67.
The higher value represents a higher quality of life in disease-related symptoms.
|
From the date of randomization (Baseline) to Cycle 2 Day 1 (Month 2)
|
Quality of Life & Disease-Related Symptoms - Physical Functioning
Time Frame: From the date of randomization (Baseline) to Cycle 2 Day 1 (Month 2)
|
Changes from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer 30-Item - Physical Functioning.
For the ripretinib arm, the minimum and maximum for the outcome were -33 to 53; the placebo arm had a range of -47 to 20.
The higher value represents a higher quality of life in disease-related symptoms.
|
From the date of randomization (Baseline) to Cycle 2 Day 1 (Month 2)
|
Quality of Life & Disease-Related Symptoms - EuroQol Visual Analogue Scale
Time Frame: From the date of randomization (Baseline) to Cycle 2 Day 1 (Month 2)
|
Change from baseline in EuroQol Visual Analogue Scale.
For the ripretinib arm the minimum and maximum for the outcome were -43 to 91; the placebo arm had a range of -68 to 23.
The higher value represents a higher quality of life in disease-related symptoms.
|
From the date of randomization (Baseline) to Cycle 2 Day 1 (Month 2)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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. Erratum In: Lancet Oncol. 2020 Jul;21(7):e341.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
February 27, 2018
Primary Completion (ACTUAL)
May 31, 2019
Study Completion (ACTUAL)
May 11, 2022
Study Registration Dates
First Submitted
November 20, 2017
First Submitted That Met QC Criteria
November 21, 2017
First Posted (ACTUAL)
November 27, 2017
Study Record Updates
Last Update Posted (ACTUAL)
November 21, 2022
Last Update Submitted That Met QC Criteria
November 17, 2022
Last Verified
November 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- DCC-2618-03-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Gastrointestinal Stromal Tumors
-
Washington University School of MedicineNorthwestern UniversityCompletedGastrointestinal Stromal Cell Tumors | Foregut Subepithelial LesionsUnited States
-
Centre Leon BerardGustave Roussy, Cancer Campus, Grand ParisCompletedSarcoma | Gastro-intestinal Stromal Tumors (GIST)France
-
AB ScienceCompletedGastro Intestinal Stromal TumorFrance
-
Centre Leon BerardRecruiting
-
Institut BergoniéFrench Sarcoma GroupRecruitingGastro Intestinal Stromal TumorFrance
-
University Medical Center GroningenDutch Cancer SocietyRecruitingGastro-intestinal Stromal TumorNetherlands
-
AB ScienceCompletedGastro-intestinal Stromal TumoursFrance
-
National University Hospital, SingaporeUnknownAsian Patients With Advanced Gastro-intestinal Stromal Tumors (GIST) Treated With ImatinibSingapore
-
Blueprint Medicines CorporationCompletedGastrointestinal Stromal Tumors (GIST) | Other Relapsed or Refractory Solid TumorsUnited States, United Kingdom, France, Korea, Republic of, Belgium, Germany, Italy, Netherlands, Poland, Spain
-
Institut BergoniéCompletedAdvanced Gastrointestinal Stromal TumorsFrance
Clinical Trials on Placebo Oral Tablet
-
EstetraICON Clinical ResearchCompletedVasomotor Symptoms | Menopausal SymptomsUnited States, Canada
-
EicOsis Human Health Inc.RecruitingHealthy SubjectsNew Zealand
-
Harmony Biosciences, LLCActive, not recruitingMyotonic Dystrophy 1 | Excessive Daytime SleepinessUnited States, Canada
-
Syntrix Biosystems, Inc.National Institute on Drug Abuse (NIDA); DF/Net ResearchCompletedDiabetic Neuropathies | Neuropathic Pain | Pain, ChronicUnited States
-
University of OxfordNovo Nordisk A/SRecruitingDiabetes Mellitus, Type 2United Kingdom
-
Fulcrum TherapeuticsTerminated
-
EicOsis Human Health Inc.CompletedHealthy AdultsUnited States
-
The Mind Research NetworkTerminatedSmoking Cessation | Tobacco Use DisorderUnited States
-
Cara Therapeutics, Inc.CompletedChronic Kidney Diseases | PruritusUnited States
-
Sunshine Lake Pharma Co., Ltd.CompletedChronic Hepatitis CChina