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Efficacy and Safety of Dovitinib in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib (MACS1755)

This study is currently recruiting participants.
Verified January 2013 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01478373
First received: November 16, 2011
Last updated: January 24, 2013
Last verified: January 2013
History of Changes
  Purpose

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


Condition Intervention Phase
Gastrointestinal Stromal Tumors
 Drug: Dovitinib (TKI258)
 Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer
U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Antitumor activity of Dovitinib in terms of disease control rate (DCR): CR+PR+SD [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Progression-free survival (PFS) of patients treated with Dovitinib [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    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.

  • Time to treatment failure (TTF)of patients treated with Dovitinib [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    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'.

  • Duration of response or stable disease [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    Duration of response or stable disease: time from the date of entry into the study to the earliest date of the first objective tumor progression or death.

  • Time to tumor progression (TTP)of patients treated with Dovitinib [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    TTP: time from the date of entry into the study to first documentation of tumor progression or death due to the underlying cancer.

  • Overall response rate (ORR)of patients treated with Dovitinib [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
    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).

  • Overall survival (OS)of patients treated with Dovitinib [ Time Frame: 21 months (9 months of estimated treatment plus 12 months of survival follow up) ] [ Designated as safety issue: No ]
    Outcome Measure Description: OS: 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.


Estimated Enrollment: 35
Study Start Date: January 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 800mg/day or patients with unresectable and/or metastatic GIST who are intolerant to 800 mg/day or less of 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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01478373

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

Locations
Belgium
Novartis Investigative Site Recruiting
Bruxelles, Belgium, 1000
Finland
Novartis Investigative Site Recruiting
HUS, Finland, FIN-00029
France
Novartis Investigative Site Recruiting
Bordeaux, France, 33076
Novartis Investigative Site Recruiting
Lille Cedex, France, 59020
Novartis Investigative Site Recruiting
Lyon Cedex, France, 69373
Novartis Investigative Site Recruiting
Reims, France, 51092
Novartis Investigative Site Recruiting
Villejuif Cedex, France, 94805
Germany
Novartis Investigative Site Recruiting
Bad Saarow, Germany, 155226
Novartis Investigative Site Recruiting
Essen, Germany, 45147
Novartis Investigative Site Recruiting
Muenchen, Germany, 81377
Italy
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20133
Novartis Investigative Site Recruiting
Roma, RM, Italy, 00168
Novartis Investigative Site Recruiting
Candiolo, TO, Italy, 10060
Novartis Investigative Site Recruiting
Torino, TO, Italy, 10153
Spain
Novartis Investigative Site Recruiting
Barcelona, Cataluna, Spain, 08025
Novartis Investigative Site Recruiting
Barcelona, Cataluna, Spain, 08035
Novartis Investigative Site Recruiting
Hospitalet de LLobregat, Catalunya, Spain, 08907
Novartis Investigative Site Recruiting
Palma De Mallorca, Islas Baleares, Spain, 07120
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Director: Study Director Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01478373     History of Changes
Other Study ID Numbers: CTKI258AIC02, 2011-001725-24
Study First Received: November 16, 2011
Last Updated: January 24, 2013
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: Ethics Committee
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Finland: Finnish Medicines Agency
Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Novartis:
GIST
Dovitinib

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
 Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 21, 2013