Gastrointestinal Stromal TumorsPhase 2NCT01478373
Efficacy and Safety of Dovitinib in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib
A Phase 2 study testing Dovitinib (TKI258) in people with Gastrointestinal Stromal Tumors, run by Novartis Pharmaceuticals at 15 sites in 5 countries.
Trial summary
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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Stromal Tumors
- What is being tested?
- Dovitinib (TKI258)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 15 sitesin 5 countries
- Study dates
- Jan 2012to Jul 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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.
Trial locations and contacts
15 sites in 5 countries.
15 sites in 5 countries
France5 sites
Novartis Investigative Site
Bordeaux, 33076
Novartis Investigative Site
Lille, 59020
Novartis Investigative Site
Lyon, 69373
Novartis Investigative Site
Reims, 51092
Novartis Investigative Site
Villejuif, 94805
Italy4 sites
Novartis Investigative Site
Candiolo, TO, 10060
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Roma, RM, 00168
Novartis Investigative Site
Torino, TO, 10153
Spain4 sites
Novartis Investigative Site
Barcelona, Barcelona, 08041
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907
Novartis Investigative Site
Palma de Mallorca, Balearic Islands, 07120
About this study
Official title: 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
- Conditions
- Gastrointestinal Stromal Tumors
- Being tested
- Dovitinib (TKI258)
- Keywords
- GIST, Dovitinib
- Medical subject headings
- Gastrointestinal Stromal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dovitinib (TKI258)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Dovitinib (TKI258) | Experimental | 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. Receives: Drug: Dovitinib (TKI258) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Antitumor Activity of Dovitinib in Terms of Disease Control Rate (DCR): Complete Response+Partial Response +Stable Disease
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.
Measured: 12 Weeks
Secondary outcomes (7)
Progression-free Survival (PFS) of Patients Treated With Dovitinib
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.
Measured: 9 months
Time to Treatment Failure (TTF)of Patients Treated With Dovitinib
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'.
Measured: 9 months
Duration of Response or Stable Disease (SD)
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.
Measured: 9 months
Time to Tumor Progression (TTP)of Patients Treated With Dovitinib
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.
Measured: 9 months
Overall Response Rate (ORR) of Patients Treated With Dovitinib
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.
Measured: Baseline, 12 weeks
Overall Survival (OS) of Patients Treated With Dovitinib
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.
Measured: 21 months (9 months of estimated treatment plus 12 months of survival follow up)
DCR (CR+PR+SD) at the End of Treatment
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.
Measured: Up to 9 months of estimated treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2011 (estimated)
- Study startJan 2012
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Gastrointestinal Stromal TumorsStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis PharmaceuticalsStudy Director, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01478373
- Sponsor's protocol ID
- CTKI258AIC02
- Other IDs
- 2011-001725-24
- Status last verified
- Apr 2016
- First submitted
- 16 Nov 2011
- Last updated
- 27 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01478373
- Acronym / sponsor ID
- CTKI258AIC02
- Conditions
- Gastrointestinal Stromal Tumors
- Keywords
- GIST, Dovitinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jan 2012
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 23 Nov 2011 (estimated)
- Results
- Posted 10 Aug 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dovitinib (TKI258) | Experimental | Drug: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dovitinib (TKI258)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. | Drug | Dovitinib (TKI258) |
Primary outcome
Antitumor Activity of Dovitinib in Terms of Disease Control Rate (DCR): Complete Response+Partial Response +Stable Disease
Time frame: 12 Weeks
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.
7 secondary outcomes
Progression-free Survival (PFS) of Patients Treated With Dovitinib
Time frame: 9 months
Time to Treatment Failure (TTF)of Patients Treated With Dovitinib
Time frame: 9 months
Duration of Response or Stable Disease (SD)
Time frame: 9 months
Time to Tumor Progression (TTP)of Patients Treated With Dovitinib
Time frame: 9 months
Overall Response Rate (ORR) of Patients Treated With Dovitinib
Time frame: Baseline, 12 weeks
Overall Survival (OS) of Patients Treated With Dovitinib
Time frame: 21 months (9 months of estimated treatment plus 12 months of survival follow up)
DCR (CR+PR+SD) at the End of Treatment
Time frame: Up to 9 months of estimated treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
Study Director study director
Novartis Pharmaceuticals
15 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dovitinib (TKI258) in people with Gastrointestinal Stromal Tumors, run by Novartis Pharmaceuticals at 15 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in France, Italy, Spain, Finland, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Antitumor Activity of Dovitinib in Terms of Disease Control Rate (DCR): Complete Response+Partial Response +Stable Disease (time frame: 12 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2016.