Clinical trial NCT01478373: Efficacy and Safety of Dovitinib in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastrointestinal Stromal Tumors
Keywords: GIST
Dovitinib
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-11-23
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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.

Primary outcomes:
measure: Antitumor Activity of Dovitinib in Terms of Disease Control Rate (DCR): Complete Response+Partial Response +Stable Disease
timeFrame: 12 Weeks
Secondary outcomes:
measure: Progression-free Survival (PFS) of Patients Treated With Dovitinib
timeFrame: 9 months
measure: Time to Treatment Failure (TTF)of Patients Treated With Dovitinib
timeFrame: 9 months
measure: Duration of Response or Stable Disease (SD)
timeFrame: 9 months
measure: Time to Tumor Progression (TTP)of Patients Treated With Dovitinib
timeFrame: 9 months
measure: Overall Response Rate (ORR) of Patients Treated With Dovitinib
timeFrame: Baseline, 12 weeks
measure: Overall Survival (OS) of Patients Treated With Dovitinib
timeFrame: 21 months (9 months of estimated treatment plus 12 months of survival follow up)
measure: DCR (CR+PR+SD) at the End of Treatment
timeFrame: Up to 9 months of estimated treatment
Other outcomes:
Locations:
city: HUS
country: Finland
facility: Novartis Investigative Site
city: Bordeaux
country: France
facility: Novartis Investigative Site
city: Lille Cedex
country: France
facility: Novartis Investigative Site
city: Lyon Cedex
country: France
facility: Novartis Investigative Site
city: Reims
country: France
facility: Novartis Investigative Site
city: Villejuif Cedex
country: France
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Candiolo
country: Italy
facility: Novartis Investigative Site
state: TO
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Palma De Mallorca
country: Spain
facility: Novartis Investigative Site
state: Islas Baleares
city: Barcelona
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
affiliation: Novartis Pharmaceuticals
name: Study Director
role: STUDY_DIRECTOR
References: