INVICTUS: Phase 3 Study of DCC-2618 vs Placebo in Advanced GIST Patients Who Have Been Treated With Prior Anticancer Therapies
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
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:
|
Placebo Comparator: Arm 2 Placebo |
Drug: Placebo Oral Tablet
Placebo
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
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.
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.- DCC-2618-03-001
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
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)] |
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 |
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
|
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)] |
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) |
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) |
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 |
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Ripretinib | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 26/85 (30.6%) | 26/43 (60.5%) | ||
Serious Adverse Events |
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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 |
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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
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 |
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Organization | Deciphera Pharmaceuticals, LLC |
Phone | 7812096400 |
clinicaltrials@deciphera.com |
- DCC-2618-03-001