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

Sponsor
Deciphera Pharmaceuticals LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03353753
Collaborator
(none)
129
35
2
49.1
3.7
0.1

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
129 participants
Allocation:
Randomized
Intervention Model:
Parallel 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 :
Feb 27, 2018
Actual Primary Completion Date :
May 31, 2019
Anticipated Study Completion Date :
Apr 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm 1

150 mg QD DCC-2618

Drug: DCC-2618
Oral KIT/PDGFRA kinase inhibitor
Other Names:
  • ripretinib
  • Placebo Comparator: Arm 2

    Placebo

    Drug: Placebo Oral Tablet
    Placebo

    Outcome Measures

    Primary Outcome Measures

    1. Progression-Free Survival (PFS) [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.

    Secondary Outcome Measures

    1. 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)].]

      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.

    2. 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)].]

      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.

    3. 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)].]

      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.

    4. 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)]

      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.

    5. Quality of Life & Disease-Related Symptoms - Physical Functioning [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.

    6. Quality of Life & Disease-Related Symptoms - EuroQol Visual Analogue Scale [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    1. 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 excluded.

    18. Gastrointestinal abnormalities including but not limited to:

    • inability to take oral medication

    • malabsorption syndromes

    • requirement for intravenous alimentation

    1. Any active bleeding excluding hemorrhoidal or gum bleeding.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 HonorHealth Scottsdale Arizona United States 85260
    2 University of Southern California - Norris Los Angeles California United States 90033
    3 UCLA Los Angeles California United States 90095
    4 Stanford Stanford California United States 94305
    5 Mayo Clinic - Jacksonville Jacksonville Florida United States 32224
    6 Georgia Cancer Specialists Atlanta Georgia United States 30341
    7 University of Chicago Chicago Illinois United States 60637
    8 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    9 University of Minnesota Minneapolis Minnesota United States 55455
    10 Mayo Clinic Rochester Minnesota United States 55905
    11 Columbia New York New York United States 10027
    12 MSKCC New York New York United States 10065
    13 Oregon Health & Science University Portland Oregon United States 97239
    14 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111
    15 MD Anderson Cancer Center Houston Texas United States 77030
    16 Alfred University Melbourne Australia
    17 University Hospital Leuven Leuven Belgium
    18 Cross Cancer Center Edmonton Alberta Canada
    19 Princess Margaret Hospital Toronto Canada
    20 Helsinki University Central Hospital Helsinki Finland
    21 Institut Bergonié Bordeaux France
    22 Le Centre Léon Bérard Lyon France
    23 Gustave-Roussy Villejuif France
    24 Sarcoma Center Brandenburg Brandenburg Germany
    25 University Hospital Essen Essen Germany
    26 Universitätsmedizin Mannheim Mannheim Germany
    27 Istituto Nazionale dei Tumori Milan Italy
    28 Università Campus Bio-Medico di Roma Rome Italy
    29 Leiden University Medical Center Leiden Netherlands
    30 Maria Sklodowska-Curie Memorial Cancer Center Warsaw Poland
    31 NCC Singapore Singapore 169610
    32 Vall d'Hebron Barcelona Spain
    33 Hospitalario Universitario Virgen del Rocío Seville Spain
    34 Royal Marsden London United Kingdom
    35 University of Sheffield Sheffield United Kingdom

    Sponsors and Collaborators

    • Deciphera Pharmaceuticals LLC

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Deciphera Pharmaceuticals LLC
    ClinicalTrials.gov Identifier:
    NCT03353753
    Other Study ID Numbers:
    • DCC-2618-03-001
    First Posted:
    Nov 27, 2017
    Last Update Posted:
    May 12, 2021
    Last Verified:
    Apr 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    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:

    Study Results

    Participant Flow

    Recruitment Details The first patient enrolled on 27 Feb 2018, with the last patient in (LPI) on 16 Nov 2018. The study is ongoing; Data cutoff date of 31 May 2019. Of the 129 patients enrolled in the double-blind period (ITT population), 85 patients were randomized to the ripretinib arm and 44 patients were randomized to the placebo arm.
    Pre-assignment Detail
    Arm/Group Title Ripretinib Placebo
    Arm/Group Description Ripretinib (150 mg) once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib). Ripretinib vs. Placebo 2:1 ratio Placebo once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib). Ripretinib vs. Placebo 2:1 ratio
    Period Title: Overall Study
    STARTED 85 44
    COMPLETED 46 35
    NOT COMPLETED 39 9

    Baseline Characteristics

    Arm/Group Title Ripretinib Placebo Total
    Arm/Group Description Ripretinib (150 mg) once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib). Ripretinib vs. Placebo 2:1 ratio Placebo once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib). Ripretinib vs. Placebo 2:1 ratio Total of all reporting groups
    Overall Participants 85 44 129
    Age, Customized (Count of Participants)
    18 - 64 Years
    57
    67.1%
    22
    50%
    79
    61.2%
    65 - 74 Years
    20
    23.5%
    12
    27.3%
    32
    24.8%
    75 Years or Older
    8
    9.4%
    10
    22.7%
    18
    14%
    Sex: Female, Male (Count of Participants)
    Female
    38
    44.7%
    18
    40.9%
    56
    43.4%
    Male
    47
    55.3%
    26
    59.1%
    73
    56.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    1.2%
    0
    0%
    1
    0.8%
    Not Hispanic or Latino
    76
    89.4%
    38
    86.4%
    114
    88.4%
    Unknown or Not Reported
    8
    9.4%
    6
    13.6%
    14
    10.9%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    4
    4.7%
    5
    11.4%
    9
    7%
    Black or African American
    8
    9.4%
    2
    4.5%
    10
    7.8%
    White
    64
    75.3%
    33
    75%
    97
    75.2%
    Not Reported
    8
    9.4%
    4
    9.1%
    12
    9.3%
    Other
    1
    1.2%
    0
    0%
    1
    0.8%
    Region (Count of Participants)
    US
    40
    47.1%
    20
    45.5%
    60
    46.5%
    Non-US
    45
    52.9%
    24
    54.5%
    69
    53.5%
    Number of Prior Systemic Anticancer Treatments (Count of Participants)
    3
    54
    63.5%
    27
    61.4%
    81
    62.8%
    ≥ 4
    31
    36.5%
    17
    38.6%
    48
    37.2%

    Outcome Measures

    1. Primary Outcome
    Title Progression-Free Survival (PFS)
    Description 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.
    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)].

    Outcome Measure Data

    Analysis Population Description
    ITT Population
    Arm/Group Title Ripretinib Placebo
    Arm/Group Description Ripretinib (150 mg) once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib). Placebo once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib).
    Measure Participants 85 44
    Median (95% Confidence Interval) [Weeks]
    27.6
    4.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ripretinib, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments Two-sided P-value
    Method Log Rank
    Comments Strata: prior lines of therapy (3 versus ≥4); ECOG (0 versus 1 or 2)
    Method of Estimation Estimation Parameter Hazard Ratio, log
    Estimated Value 0.15
    Confidence Interval (2-Sided) 95%
    0.09 to 0.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments Ripretinib: Placebo; based on stratified Cox Proportional Hazards Regression Model using randomization stratification factors [prior lines of therapy (3 versus ≥4); ECOG (0 versus 1 or 2)]
    2. Secondary Outcome
    Title Objective Response Rate (ORR)
    Description 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.
    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)].

    Outcome Measure Data

    Analysis Population Description
    ITT Population
    Arm/Group Title Ripretinib Placebo
    Arm/Group Description Ripretinib (150 mg) once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib). Placebo once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib).
    Measure Participants 85 44
    Number (95% Confidence Interval) [Percentage of Participants]
    9.4
    11.1%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ripretinib, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0504
    Comments Two-sided P-value
    Method Fisher Exact
    Comments
    3. Secondary Outcome
    Title Time to Tumor Progression (TTP) Based on Independent Radiologic Review
    Description 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.
    Time Frame From date of randomization to the earliest date of disease progression [through database cutoff 31-May-2019 (up to approximately 15 months)].

    Outcome Measure Data

    Analysis Population Description
    ITT Population
    Arm/Group Title Ripretinib Placebo
    Arm/Group Description Ripretinib (150 mg) once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib). Placebo once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib).
    Measure Participants 85 44
    Median (95% Confidence Interval) [Weeks]
    28
    4.1
    4. Secondary Outcome
    Title Overall Survival (OS)
    Description 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.
    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)].

    Outcome Measure Data

    Analysis Population Description
    ITT Population
    Arm/Group Title Ripretinib Placebo
    Arm/Group Description Ripretinib (150 mg) once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib). Placebo once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib).
    Measure Participants 85 44
    Median (95% Confidence Interval) [weeks]
    65.6
    28.6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ripretinib, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0004
    Comments Not evaluated for statistical significance as a result of the sequential testing procedure for the secondary endpoints of ORR and OS.
    Method Log Rank
    Comments Strata: prior lines of therapy (3 versus ≥4); ECOG (0 versus 1 or 2)
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.36
    Confidence Interval (2-Sided) 95%
    0.21 to 0.62
    Parameter Dispersion Type:
    Value:
    Estimation Comments Ripretinib: Placebo; based on stratified Cox Proportional Hazards Regression Model using randomization stratification factors [prior lines of therapy (3 versus ≥4); ECOG (0 versus 1 or 2)]
    5. Secondary Outcome
    Title Quality of Life & Disease-Related Symptoms - European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer 30-Item - Role Functioning
    Description 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.
    Time Frame From the date of randomization (Baseline) to Cycle 2 Day 1 (Month 2)

    Outcome Measure Data

    Analysis Population Description
    ITT Population
    Arm/Group Title Ripretinib Placebo
    Arm/Group Description Ripretinib (150 mg) once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib). Placebo once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib).
    Measure Participants 85 43
    Mean (Standard Deviation) [units on a scale]
    3.5
    (27.31)
    -17.1
    (30.28)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ripretinib, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments Not evaluated for statistical significance as a result of the sequential testing procedure for the secondary endpoints of ORR, OS, and QOL.
    Method ANCOVA
    Comments Factors: prior lines of therapy (3 versus ≥4); ECOG (0 versus 1 or 2)
    6. Secondary Outcome
    Title Quality of Life & Disease-Related Symptoms - Physical Functioning
    Description 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.
    Time Frame From the date of randomization (Baseline) to Cycle 2 Day 1 (Month 2)

    Outcome Measure Data

    Analysis Population Description
    ITT Population
    Arm/Group Title Ripretinib Placebo
    Arm/Group Description Ripretinib (150 mg) once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib). Placebo once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib).
    Measure Participants 85 43
    Mean (Standard Deviation) [units on a scale]
    1.6
    (16.03)
    -8.9
    (19.28)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ripretinib, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments Not evaluated for statistical significance as a result of the sequential testing procedure for the secondary endpoints of ORR, OS, and QOL.
    Method ANCOVA
    Comments Factors: prior lines of therapy (3 versus ≥4); ECOG (0 versus 1 or 2)
    7. Secondary Outcome
    Title Quality of Life & Disease-Related Symptoms - EuroQol Visual Analogue Scale
    Description 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.
    Time Frame From the date of randomization (Baseline) to Cycle 2 Day 1 (Month 2)

    Outcome Measure Data

    Analysis Population Description
    ITT Population
    Arm/Group Title Ripretinib Placebo
    Arm/Group Description Ripretinib (150 mg) once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib). Placebo once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib).
    Measure Participants 85 43
    Mean (Standard Deviation) [Units on a Scale]
    3.7
    (20.36)
    -8.9
    (19.31)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ripretinib, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments
    Method t-test, 2 sided
    Comments

    Adverse Events

    Time Frame After Administration of the first dose of study drug and through 30 days after the last dose of study drug. A median of 28 weeks per participant for the ripretinib arm, and a median of 10 weeks per participant for the placebo arm.
    Adverse Event Reporting Description Treatment-Emergent Adverse Events (TEAEs) are defined as any adverse event (all grades) that occurs after administration of the first dose of study drug and through 30 days after the last dose of study drug (Safety Population).The median treatment duration of the safety population for ripretinib arm was 23.86 weeks and placebo was 6 weeks during the double-blind period.
    Arm/Group Title Ripretinib Placebo
    Arm/Group Description Ripretinib (150 mg) once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib). Placebo once daily in 28-day cycles until disease progression by Independent Radiologic Review (IRR) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior therapies (therapies must include treatment with imatinib, sunitinib, and regorafenib).
    All Cause Mortality
    Ripretinib Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 26/85 (30.6%) 26/43 (60.5%)
    Serious Adverse Events
    Ripretinib Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 26/85 (30.6%) 19/43 (44.2%)
    Blood and lymphatic system disorders
    Anemia 3/85 (3.5%) 1/43 (2.3%)
    Cardiac disorders
    Cardiac Failure 1/85 (1.2%) 0/43 (0%)
    Pericardial Effusion 1/85 (1.2%) 0/43 (0%)
    Gastrointestinal disorders
    Abdominal Pain 4/85 (4.7%) 2/43 (4.7%)
    Nausea 2/85 (2.4%) 0/43 (0%)
    Vomiting 2/85 (2.4%) 0/43 (0%)
    Ascites 1/85 (1.2%) 1/43 (2.3%)
    Constipation 1/85 (1.2%) 0/43 (0%)
    Duodenal Ulcer 1/85 (1.2%) 0/43 (0%)
    Fecaloma 1/85 (1.2%) 0/43 (0%)
    Gastrointestinal Fistula 1/85 (1.2%) 1/43 (2.3%)
    Gastroesophageal Reflux Disease 1/85 (1.2%) 0/43 (0%)
    Small Intestinal Obstruction 1/85 (1.2%) 1/43 (2.3%)
    Upper Gastrointestinal Hemorrhage 1/85 (1.2%) 0/43 (0%)
    Gastrointestinal Perforation 0/85 (0%) 1/43 (2.3%)
    General disorders
    Death 3/85 (3.5%) 4/43 (9.3%)
    General Physical Health Deterioration 1/85 (1.2%) 0/43 (0%)
    Asthenia 0/85 (0%) 2/43 (4.7%)
    Pyrexia 0/85 (0%) 1/43 (2.3%)
    Systemic Inflammatory Response Syndrome 0/85 (0%) 1/43 (2.3%)
    Infections and infestations
    Liver Abscess 1/85 (1.2%) 0/43 (0%)
    Sepsis 1/85 (1.2%) 2/43 (4.7%)
    Upper Respiratory Tract Infection 1/85 (1.2%) 0/43 (0%)
    Urinary Tract Infection 1/85 (1.2%) 1/43 (2.3%)
    Septic Shock 0/85 (0%) 1/43 (2.3%)
    Injury, poisoning and procedural complications
    Facial Bones Fracture 0/85 (0%) 1/43 (2.3%)
    Investigations
    Blood Bilirubin Increased 1/85 (1.2%) 0/43 (0%)
    Blood Creatinine Increased 0/85 (0%) 1/43 (2.3%)
    Metabolism and nutrition disorders
    Hyperkaliemia 1/85 (1.2%) 1/43 (2.3%)
    Hypoglycemia 1/85 (1.2%) 0/43 (0%)
    Hypophosphatasemia 1/85 (1.2%) 0/43 (0%)
    Dehydration 0/85 (0%) 1/43 (2.3%)
    Musculoskeletal and connective tissue disorders
    Musculoskeletal Chest Pain 1/85 (1.2%) 0/43 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumor pain 0/85 (0%) 1/43 (2.3%)
    Psychiatric disorders
    Hallucinations, mixed 1/85 (1.2%) 0/43 (0%)
    Mental Status Changes 1/85 (1.2%) 0/43 (0%)
    Renal and urinary disorders
    Acute Kidney Injury 1/85 (1.2%) 2/43 (4.7%)
    Urinary Retention 0/85 (0%) 1/43 (2.3%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 1/85 (1.2%) 0/43 (0%)
    Hemoptysis 0/85 (0%) 1/43 (2.3%)
    Pulmonary Edema 0/85 (0%) 1/43 (2.3%)
    Vascular disorders
    Embolism 1/85 (1.2%) 0/43 (0%)
    Other (Not Including Serious) Adverse Events
    Ripretinib Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 84/85 (98.8%) 42/43 (97.7%)
    Blood and lymphatic system disorders
    Anemia 12/85 (14.1%) 8/43 (18.6%)
    Gastrointestinal disorders
    Nausea 33/85 (38.8%) 5/43 (11.6%)
    Abdominal Pain 31/85 (36.5%) 13/43 (30.2%)
    Constipation 29/85 (34.1%) 8/43 (18.6%)
    Diarrhea 24/85 (28.2%) 6/43 (14%)
    Vomiting 18/85 (21.2%) 3/43 (7%)
    Stomatitis 9/85 (10.6%) 0/43 (0%)
    Abdominal Pain (Upper) 8/85 (9.4%) 2/43 (4.7%)
    Dyspepsia 7/85 (8.2%) 6/43 (14%)
    General disorders
    Fatigue 36/85 (42.4%) 10/43 (23.3%)
    Peripheral Edema 14/85 (16.5%) 3/43 (7%)
    Asthenia 11/85 (12.9%) 6/43 (14%)
    Pyrexia 6/85 (7.1%) 2/43 (4.7%)
    Investigations
    Weight Decreased 16/85 (18.8%) 5/43 (11.6%)
    Blood Bilirubin Increased 14/85 (16.5%) 0/43 (0%)
    Lipase Increased 9/85 (10.6%) 0/43 (0%)
    Aspartate Aminotransferase Increased 6/85 (7.1%) 2/43 (4.7%)
    Blood Alkaline Phosphatase Increased 6/85 (7.1%) 1/43 (2.3%)
    Alanine Aminotransferase Increased 5/85 (5.9%) 1/43 (2.3%)
    Metabolism and nutrition disorders
    Decreased Appetite 23/85 (27.1%) 9/43 (20.9%)
    Hypophosphatemia 9/85 (10.6%) 0/43 (0%)
    Hypokalemia 5/85 (5.9%) 1/43 (2.3%)
    Musculoskeletal and connective tissue disorders
    Myalgia 27/85 (31.8%) 5/43 (11.6%)
    Arthralgia 15/85 (17.6%) 2/43 (4.7%)
    Muscle Spasms 13/85 (15.3%) 2/43 (4.7%)
    Back Pain 8/85 (9.4%) 2/43 (4.7%)
    Pain in Extremity 8/85 (9.4%) 2/43 (4.7%)
    Musculoskeletal pain 5/85 (5.9%) 3/43 (7%)
    Nervous system disorders
    Headache 16/85 (18.8%) 2/43 (4.7%)
    Dizziness 7/85 (8.2%) 3/43 (7%)
    Peripheral Sensory Neuropathy 6/85 (7.1%) 1/43 (2.3%)
    Psychiatric disorders
    Insomnia 8/85 (9.4%) 6/43 (14%)
    Anxiety 7/85 (8.2%) 4/43 (9.3%)
    Depression 6/85 (7.1%) 0/43 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 11/85 (12.9%) 0/43 (0%)
    Cough 6/85 (7.1%) 1/43 (2.3%)
    Skin and subcutaneous tissue disorders
    Alopecia 44/85 (51.8%) 2/43 (4.7%)
    Palmar-Plantar Erythrodysesthesia Syndrome 18/85 (21.2%) 0/43 (0%)
    Dry Skin 11/85 (12.9%) 3/43 (7%)
    Pruritus 9/85 (10.6%) 2/43 (4.7%)
    Actinic keratosis 5/85 (5.9%) 1/43 (2.3%)
    Dermatitis Acneiform 5/85 (5.9%) 0/43 (0%)
    Hyperkeratosis 5/85 (5.9%) 0/43 (0%)
    Pruritus Generalized 5/85 (5.9%) 1/43 (2.3%)
    Rash Maculo-Papular 5/85 (5.9%) 0/43 (0%)
    Vascular disorders
    Hypertension 12/85 (14.1%) 2/43 (4.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Neither Institution nor Investigator will submit for publication or public disclosure any publication or disclosure based on the results of the Study until after the first to occur of (a) publication of the Multi-Center Clinical Trial results; (b) notification by Sponsor that the Multi-Center Clinical Trial submission is no longer planned; or (c) the 12 month anniversary of the completion or early termination of the Multi-Center Clinical Trial.

    Results Point of Contact

    Name/Title INVICTUS Clinical Team
    Organization Deciphera Pharmaceuticals, LLC
    Phone 7812096400
    Email clinicaltrials@deciphera.com
    Responsible Party:
    Deciphera Pharmaceuticals LLC
    ClinicalTrials.gov Identifier:
    NCT03353753
    Other Study ID Numbers:
    • DCC-2618-03-001
    First Posted:
    Nov 27, 2017
    Last Update Posted:
    May 12, 2021
    Last Verified:
    Apr 1, 2021