Dovigist : Phase II trial to evaluate the treatment benefits and the safety of the new investigational medicine Dovitinib (TKI258) in patients with specific cancers in the gastrointestinal tract which do not respond any more to the currently established standard treatment imatinib or can not be treated any more with imatinib because of intolerance.
- Conditions
- nresectable, metastatic or recurrent gastrointestinal stromal tumor (GIST)MedDRA version: 15.0Level: LLTClassification code 10062427Term: Gastrointestinal stromal tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-001725-24-FI
- Lead Sponsor
- ovartis Pharma Services
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 29
Patients eligible for inclusion in this study have to meet all of the following criteria
- Male or female patients = 18 years of age
- 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 on KIT or PDGFRA genes
- 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).
- A performance status of 0, 1 or 2 according to ECOG
- Recovery from Grade 2 to 4 toxicity related to prior imatinib assessed according to NCI-CTCAE v.4.0
- Adequate bone marrow function
- Adequate liver function
- Adequate renal function
Other protocol-defined inclusion criteria may apply
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 11
- Patients who have received any other tyrosine-kinase inhibitor but imatinib for GIST
- Use of any investigational agent within 28 days prior to starting Dovitinib (TKI258) or foreseen use of an investigational agent during the study
- Imatinib must be discontinued at least 5 days before first dose of Dovitinib (TKI258)
- 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
- Patients with another primary malignancy within 3 years prior to starting the study drug, with the exception of adequately treated in-situ carcinoma of the uterine cervix, or completely excised (R0 resection) basal or squamous cell carcinoma of the skin
- Patients who have undergone major surgery 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 certain QT-related medicinal conditions
- Patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of Dovitinib
- Uncontrolled hypertension
- Patients with any clinically significant medical or surgical condition which should preclude participation
- Known diagnosis of human immunodeficiency virus (HIV) infection. HIV testing is not mandatory
- Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin or equivalent anticoagulant
- Pregnant or breast-feeding women
- Women of child-bearing potential not employing two highly effective methods of birth control having at least onefailure ratio < 1%.
- Fertile males not willing to use contraception
Other protocol-defined exclusion criteria may apply
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the antitumor activity of Dovitinib (TKI258) in terms of disease control rate (DCR):<br>CR+PR+SD, at 12 weeks in adult patients with documented disease progression while on<br>therapy with imatinib for unresectable and/or metastatic GIST, recurrent GIST on adjuvant<br>imatinib or within the first 3 months after discontinuation of adjuvant imatinib or, unresectable<br>and/or metastatic GIST intolerant to imatinib;Secondary Objective: Secondary objectives: to assess<br>- Progression-free survival (PFS)<br>- Time to treatment failure (TTF)<br>- Duration of response or stable disease<br>- Time to progression (TTP)<br>- Overall response rate (ORR)<br>- Overall survival (OS)<br>- Safety and tolerability of Dovitinib (TKI258);Primary end point(s): Disease control rate defined as the proportion of patients with a best overall response of CR, PR and SD at 12 weeks according to RECIST.;Timepoint(s) of evaluation of this end point: 12 weeks after the first dose of study drug.
- Secondary Outcome Measures
Name Time Method