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

NCT01478373 | Completed Phase 2 Results

• 2 other identifiers: CTKI258AIC022011-001725-24
• Study Type: interventional
• Target: 39
• Locations: 5 countries
• Sites: 15

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

Conditions

Gastrointestinal Stromal Tumors

Keywords

GIST; Dovitinib

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (7)

• Progression-free Survival (PFS) of Patients Treated With Dovitinib

  9 months

• Time to Treatment Failure (TTF)of Patients Treated With Dovitinib

  9 months

• Duration of Response or Stable Disease (SD)

  9 months

• Time to Tumor Progression (TTP)of Patients Treated With Dovitinib

  9 months

• Overall Response Rate (ORR) of Patients Treated With Dovitinib

  Baseline, 12 weeks

Study Arms (1)

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.

Drug: Dovitinib (TKI258)

Interventions

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.

Dovitinib (TKI258)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (15)

Novartis Investigative Site

HUS, FIN-00029, Finland

Location

Novartis Investigative Site

Bordeaux, 33076, France

Location

Novartis Investigative Site

Lille, 59020, France

Location

Novartis Investigative Site

Lyon, 69373, France

Location

Novartis Investigative Site

Reims, 51092, France

Location

Novartis Investigative Site

Villejuif, 94805, France

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Roma, RM, 00168, Italy

Location

Novartis Investigative Site

Candiolo, TO, 10060, Italy

Location

Novartis Investigative Site

Torino, TO, 10153, Italy

Location

Novartis Investigative Site

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Novartis Investigative Site

Barcelona, Barcelona, 08041, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

• Study Director

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2011
• First Posted: November 23, 2011
• Study Start: January 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: April 27, 2016
• Results First Posted: August 10, 2015

Record last verified: 2016-04

Locations

FR (5); FI (1); DE (1); ES (4); IT (4)