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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01478373
First received: November 16, 2011
Last updated: December 20, 2013
Last verified: December 2013

November 16, 2011
December 20, 2013
January 2012
June 2014   (final data collection date for primary outcome measure)
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).
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 Respones (CR), Partial Response (PR) and Stable Disease (SD) at 12 weeks according to RECIST (version 1.1).
Complete list of historical versions of study NCT01478373 on ClinicalTrials.gov Archive Site
  • 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.
  • DCR (CR+PR+SD) at the end of treatment [ Time Frame: end of treatment ] [ Designated as safety issue: No ]
    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).
  • Safety and tolerability of Dovitinib (TKI258) [ Time Frame: duration of treatment ] [ Designated as safety issue: Yes ]
    Incidence of adverse events (AEs), serious adverse events (SAEs) and abnormal laboratory results (hematology, blood chemistry) will be assessed by the Common Terminology Criteria for Adverse Events (CTCAE), v4.0.
  • 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.
Not Provided
Not Provided
 
Efficacy and Safety of Dovitinib in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib
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

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

Not Provided
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Gastrointestinal Stromal Tumors
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.
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.
Intervention: Drug: Dovitinib (TKI258)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
39
June 2014
June 2014   (final data collection date for primary outcome measure)

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.

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France,   Germany,   Italy,   Spain
 
NCT01478373
CTKI258AIC02, 2011-001725-24
No
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Director: Study Director Novartis Pharmaceuticals
Novartis
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP