- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01478373
Efficacy and Safety of Dovitinib in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib
April 26, 2016 updated by: Novartis Pharmaceuticals
DOVIGIST: Phase II Trial to Evaluate the Efficacy and Safety of Dovitinib (TKI258) in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib
The purpose of this study is to evaluate the efficacy and safety of Dovitinib in patients with gastrointestinal stromal tumors refractory and/or intolerant to Imatinib
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
39
Phase
- Phase 2
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
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HUS, Finland, FIN-00029
- Novartis Investigative Site
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Bordeaux, France, 33076
- Novartis Investigative Site
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Lille Cedex, France, 59020
- Novartis Investigative Site
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Lyon Cedex, France, 69373
- Novartis Investigative Site
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Reims, France, 51092
- Novartis Investigative Site
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Villejuif Cedex, France, 94805
- Novartis Investigative Site
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Essen, Germany, 45147
- Novartis Investigative Site
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MI
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Milano, MI, Italy, 20133
- Novartis Investigative Site
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RM
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Roma, RM, Italy, 00168
- Novartis Investigative Site
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TO
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Candiolo, TO, Italy, 10060
- Novartis Investigative Site
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Torino, TO, Italy, 10153
- Novartis Investigative Site
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Barcelona, Spain, 08041
- Novartis Investigative Site
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Catalunya
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Barcelona, Catalunya, Spain, 08035
- Novartis Investigative Site
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Hospitalet de LLobregat, Catalunya, Spain, 08907
- Novartis Investigative Site
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Islas Baleares
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Palma De Mallorca, Islas Baleares, Spain, 07120
- Novartis Investigative Site
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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:
- Histologically confirmed GIST of any anatomical location, which is 1) unresectable and/ or metastatic with documented disease progression while on therapy with imatinib or 2) surgically removed localized GIST, recurrent on adjuvant imatinib or recurrent within the first 3 months after discontinuation of adjuvant imatinib or 3) patients with unresectable and/or metastatic GIST intolerant to imatinib
- Positive immunohistochemical staining for c-KIT (CD117); or negative staining for KIT, but with either positive staining for DOG1 or an identified mutation of KIT or PDGFRA gene
- Documented disease progression according to RECIST (version 1.1) on prior therapy with imatinib at a dose of at least 400mg/day or patients with unresectable and/or metastatic GIST who are intolerant to imatinib
- At least one measurable GIST lesion according to RECIST (version 1.1).
- Adequate bone marrow, liver and renal function
Exclusion Criteria:
- Patients who have received any other tyrosine-kinase inhibitor but imatinib for GIST
- Patients who received cytotoxic drugs ≤ 4 weeks prior to starting Dovitinib (TKI258)
- Patients who are treated or planned to be treated concomitantly with other cytotoxic or antineoplastic treatments, such as chemotherapy, immunotherapy, biological response modifiers, or radiotherapy
- Patients with another primary malignancy within 3 years prior to starting the study drug
- Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic) ≤ 4 weeks prior to starting Dovitinib (TKI258) or who have not recovered from the adverse effects of such therapy
- Patients with a history of pulmonary embolism (PE), or untreated deep venous thrombosis (DVT) within the past 6 months
- Patients with impaired cardiac function or clinically significant cardiac diseases
- Patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of Dovitinib
- Patients with prior complete gastrectomy
- Patients with brain metastasis or history of brain metastasis
- Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin or equivalent anticoagulant
- Pregnant or breast-feeding women
Other protocol-defined inclusion/exclusion criteria may apply.
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: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Dovitinib (TKI258)
Patients will receive Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
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Oral Dovitinib (TKI258) as a gelatin capsule of 100 mg strength and dosed on a flat scale of 500 mg on a 5 days on /2 days off dosing schedule.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Antitumor Activity of Dovitinib in Terms of Disease Control Rate (DCR): Complete Response+Partial Response +Stable Disease
Time Frame: 12 Weeks
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DCR is defined as the proportion of patients with a best overall response of Complete Responses (CR), Partial Response (PR) and Stable Disease (SD) at 12 weeks according to RECIST (version 1.1).
Complete Response (CR): Disappearance of all non-nodal target lesions.
In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1;Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Progressive Disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline.
In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.
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12 Weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Progression-free Survival (PFS) of Patients Treated With Dovitinib
Time Frame: 9 months
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The PFS duration: time from entry into the study to the date of the first documented progression (assessed using conventional RECIST (version 1.1) or death due to any cause.
Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
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9 months
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Time to Treatment Failure (TTF)of Patients Treated With Dovitinib
Time Frame: 9 months
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TTF: the date of entry into the study to the earliest date of the first objective tumor progression, date of death due to any cause, or date of discontinuation due to reasons other than 'Protocol deviation' or 'Administrative problems'.
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9 months
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Duration of Response or Stable Disease (SD)
Time Frame: 9 months
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Duration of response or SD: time from date of entry into study to earliest date of first objective tumor progression or death.
DCR is defined as proportion of patients with best overall response of CR, PR and SD at 12 weeks according to RECIST (version 1.1).
CR: Disappearance of all non-nodal target lesions.
Any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1; PR: At least a 30% decrease in sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
PD: At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline.
In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.
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9 months
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Time to Tumor Progression (TTP)of Patients Treated With Dovitinib
Time Frame: 9 months
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TTP: time from the date of entry into the study to first documentation of tumor progression or death due to the underlying cancer.
Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
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9 months
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Overall Response Rate (ORR) of Patients Treated With Dovitinib
Time Frame: Baseline, 12 weeks
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Outcome Measure Description: ORR: proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST (version 1.1).
Complete Response (CR): Disappearance of all non-nodal target lesions.
In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1;Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Progressive Disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline.
In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.
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Baseline, 12 weeks
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Overall Survival (OS) of Patients Treated With Dovitinib
Time Frame: 21 months (9 months of estimated treatment plus 12 months of survival follow up)
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Outcome Measure Description: OS: time from the date of entry into the study to the date of death due to any cause.
A patient who has not died by the date of the analysis cut-off would have the OS censored at the time of the last contact before the cut-off date.
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21 months (9 months of estimated treatment plus 12 months of survival follow up)
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DCR (CR+PR+SD) at the End of Treatment
Time Frame: Up to 9 months of estimated treatment
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DCR is defined as the proportion of patients with a best overall response of CR, PR and SD at the end of dovitinib treatment according to RECIST (version 1.1).
Complete Response (CR): Disappearance of all non-nodal target lesions.
In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1;Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Progressive Disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline.
In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.
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Up to 9 months of estimated treatment
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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
January 1, 2012
Primary Completion (Actual)
July 1, 2014
Study Completion (Actual)
July 1, 2014
Study Registration Dates
First Submitted
November 16, 2011
First Submitted That Met QC Criteria
November 21, 2011
First Posted (Estimate)
November 23, 2011
Study Record Updates
Last Update Posted (Estimate)
April 27, 2016
Last Update Submitted That Met QC Criteria
April 26, 2016
Last Verified
April 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CTKI258AIC02
- 2011-001725-24 (EudraCT Number)
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.
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