Clinical Trial: Dovitinib in Treating Patients With Recurrent or Progressive Glioblastoma

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Phase II Study of TKI258 (Dovitinib) in Patients With Recurrent or Progressive Glioblastoma Who Have Progressed With or Without Anti-Angiogenic Therapy (Including Anti-VEGF Therapy)

Brief Summary: This phase II trial studies how well dovitinib works in treating patients with recurrent or progressive glioblastoma. Dovitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

Detailed Summary:

PRIMARY OBJECTIVES:

Arm 1: To determine 6 month progression-free survival (PFS6) in anti-angiogenic therapy (including anti-VEGF therapy or bevacizumab) naive patients with recurrent glioblastoma (GBM) in patients treated with dovitinib

Arm 2: To estimate time to progression in patients with recurrent or progressive Glioblastoma who have progressed on anti-angiogenic therapy (including anti-VEGF therapy).

SECONDARY OBJECTIVES:

  1. To evaluate the side effect profile of dovitinib in both patient populations.
  2. To evaluate the efficacy of dovitinib as measured by objective response rate (ORR) in both patient populations.
  3. To estimate time to percentage of patients free from progression at 6 months (PFS-6)in patients with recurrent or progressive Glioblastoma who have progressed on antiangiogenic therapy (including anti-VEGF therapy).
  4. To estimate time to progression in anti-angiogenic therapy (including anti-VEGF therapy or bevacizumab) naiVe patients with recurrent glioblastoma (GBM) in patients treated with dovitinib,
  5. To evaluate the overall survival (OS) in both patient populations.

EXPLORATORY OBJECTIVES:

To explore association between clinical outcome and potential biomarkers that may include microparticles, PlGF, PDGF-AA, PDGF-AB, PDGF-BB, SDF-1a, thrombospondin-1, Ang1, and Il-6, IL-8 and FGF.

OUTLINE:

Patients receive dovitinib orally (PO) 5 days a week.
Sponsor: Manmeet Ahluwalia, MD

Current Primary Outcome:

  • Arm 1: Progression Free Survival (PFS) [ Time Frame: 6 months ]
    Number of anti-angiogenic therapy (including anti-VEGF therapy or bevacizumab) naive patients with recurrent glioblastoma (GBM). The Kaplan-Meier method will be used. The progression- free survival (PFS) at 6 months is defined as the time from randomization to objective tumor progression or death. So patients who have CR, PR or SD at 6 months will constitute PFS-6.
  • Arm 2: Determine median time to progression [ Time Frame: at 8 weeks (2 cycles of treatment) ]
    Anti-angiogenic therapy (including anti-VEGF therapy or bevacizumab) patients with recurrent glioblastoma (GBM). The Kaplan-Meier method will be used. Time to tumor progression (TTP), is defined as the time from randomization to time of progressive disease. So it is ongoing and will be assessed every 8 weeks …8, 16, 24, 32 …week.


Original Primary Outcome: Determine median time to progression [ Time Frame: at 8 weeks (2 cycles of treatment) ]

The Kaplan-Meier method will be used. Time to tumor progression (TTP), is defined as the time from randomization to time of progressive disease. So it is ongoing and will be assessed every 8 weeks …8, 16, 24, 32 …week.


Current Secondary Outcome:

  • Toxicity assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 30 days after treatment ]
    Number of patients in both populations that experience toxicity (grade 1-5).
  • Objective response rate using modified Revised Assessment in Neuro-Oncology (RANO) criteria [ Time Frame: Up to 30 days after treatment ]
    Number of patients (both populations) with a complete response (CR-no measurable disease), partial response (PR >50% reduction in measurable disease), minor response (MR >25% reduction of measurable disease), stable disease (SD <25% reduction) and progressive disease (PD >25% measurable disease and new lesions).
  • Number of anti-angiogenic therapy patients with progression free survival [ Time Frame: 6 months ]
    The progression- free survival (PFS) at 6 months is defined as the time from randomization to objective tumor progression or death. So patients who have CR, PR or SD at 6 months will constitute PFS-6
  • Overall survival [ Time Frame: to death, approximately 2 years ]
    The Kaplan-Meier method will be used. Overall survival is defined as the time from randomization to death.


Original Secondary Outcome:

  • Toxicity assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 30 days after treatment ]
    Number of patients that experience toxicity (grade 1-5).
  • Objective response rate using modified Revised Assessment in Neuro-Oncology (RANO) criteria [ Time Frame: Up to 30 days after treatment ]
    Number of patients with a complete response (no measurable disease), partial response (>50% reduction in measurable disease), minor response (>25% reduction of measurable disease), stable disease (<25% reduction) and progressive disease (>25% measurable disease and new lesions).
  • Number of patients with progression free survival [ Time Frame: 6 months ]
    The progression- free survival (PFS) at 6 months is defined as the time from randomization to objective tumor progression or death. So patients who have CR, PR or SD at 6 months will constitute PFS-6
  • Overall survival [ Time Frame: to death, approximately 2 years ]
    The Kaplan-Meier method will be used. Overall survival is defined as the time from randomization to death.


Information By: Case Comprehensive Cancer Center

Dates:
Date Received: December 18, 2012
Date Started: December 2012
Date Completion: May 2016
Last Updated: November 2, 2015
Last Verified: November 2015