Efficacy and Safety of Dovitinib in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib

Gastrointestinal Stromal Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01478373
• Other study ID #: CTKI258AIC02
• Secondary ID: 2011-001725-24
• Status: Completed
• Phase: Phase 2
• First received: November 16, 2011
• Last updated: April 26, 2016
• Start date: January 2012
• Est. completion date: July 2014

Study information

• Verified date: April 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Italy: Ethics CommitteeSpain: Agencia Española de Medicamentos y Productos SanitariosFinland: Finnish Medicines AgencyBelgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumors

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Finland	Novartis Investigative Site	HUS
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Lyon Cedex
France	Novartis Investigative Site	Reims
France	Novartis Investigative Site	Villejuif Cedex
Germany	Novartis Investigative Site	Essen
Italy	Novartis Investigative Site	Candiolo	TO
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Torino	TO
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya
Spain	Novartis Investigative Site	Palma De Mallorca	Islas Baleares

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Finland,  France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12 Weeks	No
Secondary	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.	9 months	No
Secondary	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'.	9 months	No
Secondary	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.	9 months	No
Secondary	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.	9 months	No
Secondary	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.	Baseline, 12 weeks	No
Secondary	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.	21 months (9 months of estimated treatment plus 12 months of survival follow up)	No
Secondary	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.	Up to 9 months of estimated treatment	No