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Ph I SU011248 + Irinotecan in Treatment of Pts w MG

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00611728
Recruitment Status : Completed
First Posted : February 11, 2008
Last Update Posted : July 21, 2014
Information provided by (Responsible Party):
Duke University

Brief Summary:
Primary Objectives To determine maxi tolerated dose & dose limiting toxicity of SU011248 + Irinotecan in recurrent MG pts not on EIAEDs To characterize safety & tolerability of SU011248 + Irinotecan among pts w recurrent MG Secondary Objectives To evaluate pharmacokinetic profile of SU011248 & Irinotecan when co-administered in pts w MG To evaluate anti-tumor activity of SU011248 + Irinotecan

Condition or disease Intervention/treatment Phase
Glioblastoma Drug: SU011248 & Irinotecan Phase 1

Detailed Description:

Primary interest for combining SU011248 w irinotecan in malignant glioma pts derives from dramatic anti-tumor activity recently demonstrated among RMG pts treated w humanized anti-VEGF monoclonal antibody, bevacizumab, when combined w irinotecan. 63 percent radiographic response rate was observed following treatment w regimen every other wk, & median progression-free survival was 23wks. Similar enhancement of chemo activity by VEGF-directed therapy w bev has been previously demonstrated for colorectal & lung cancer pts. SU011248 is being evaluated in current regimen because it may exert more potent anti-angiogenic effect than bev among MG pts due to its ability to inhibit PDGFR-mediated pericyte stabilization in tumor neovasculature.

Current proposed ph I study is designed to determine MTD & DLT of SU011248 when combo w irinotecan for pts w RMG. Both SU01148 & irinotecan are known to be metabolized by CYP3A4 cytochrome system. Current study will limit enrollment to pts who are not on CYP3A4-enzyme inducing anti-epileptic drugs.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of SU011248 Plus Irinotecan in the Treatment of Patients With Malignant Glioma
Study Start Date : March 2008
Actual Primary Completion Date : June 2010
Actual Study Completion Date : September 2010

Intervention Details:
  • Drug: SU011248 & Irinotecan

    Sutent given in daily oral manner for 1st 4 wks of each 6wk cycle. You will not take any Sutent during last 14 days of each 6 wk cycle. CPT-11 will be given intravenously over 1 & 1/2 hrs on 1st day of each cycle & then again on days 14 & 28.

    Sutent is approved for adult subjects w some forms of kidney cancer. It is considered "investigational" for brain tumors. Dosing will begin on day 1 of cycle 1 & continue daily for 4 wks by mouth.

    Irinotecan is approved for adult subjects with some forms of colorectal cancer. It is also considered "investigational" for brain tumors. Irinotecan dose will depend on your height & weight. Irinotecan will be given intravenously over 90 min on days 1, 14 & 28 of 6wk cycle.

    You will be seen in clinic approximately every 42 days for 1st 3 cycles of study drug, & then every other cycle thereafter. Your brain MRI examination will be done within 1 wk prior to completion of cycles 1-3, & then within 1 week prior to completion of every other cycle.

    Other Names:
    • SU011248-Sutent-Sunitinib
    • Irinotecan-CPT 11-Camptosar

Primary Outcome Measures :
  1. Determine MTD & DLT of SU011248 + Irinotecan in pts w RMG not on EIAEDs [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Demographic & baseline characteristics [ Time Frame: 6 months ]
  2. Efficacy observations & measurements [ Time Frame: 6 months ]
  3. Safety observations & measurements [ Time Frame: 6 months ]
  4. PK measurements [ Time Frame: 6 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Pts confirmed GBM, GS, AA, AO & AOA w recurrent disease following standard therapy consisting of at least external beam XRT & temo chemo
  • Pts not had tumor biopsy <1 week/surgical resection <2 weeks prior to starting study drug
  • Pts should be on non-increasing dose of steroids >7 days prior to obtaining baseline Gd-MRI of brain
  • Age >18yrs
  • KPS >70
  • ANC >1.5 x 10 9/L
  • Hgb >9 g/dL
  • Platelets >100 x 10 9/L
  • AST/SGOT & ALT/SGPT <2.5 x ULN
  • Serum bilirubin <1.5 x ULN
  • Serum CA <12 mg/dL
  • Serum creatinine <1.5 x ULN/measured 24-hr CrCl>50mL/min/1.73m^2
  • Pt has ability to understand & provide signed informed consent that fulfills IRB guidelines

Exclusion Criteria:

  • Prior gr3/>toxicity/failure to CPT-11 therapy
  • Prior Sunitinib malate therapy
  • Concurrent administration of EIAEDs
  • Major surgery <2 weeks of enrollment
  • History of impaired cardiac function
  • Other clinically significant cardiac diseases
  • Uncontrolled diabetes
  • Active/uncontrolled infection requiring intravenous antibiotics
  • Impairment of GI function/GI disease that may significantly alter absorption of Sunitinib malate Sutent
  • Acute/chronic liver/renal disease
  • Cerebrovascular accident/transient ischemic attack <6mths of study enrollment
  • Pulmonary embolism <6mths of study enrollment
  • Pre-existing thyroid abnormality w thyroid function that can not be maintained in normal range w medication
  • Pts taking warfarin sodium
  • Pts have received chemo ≤4wks to starting study drug unless they have fully recovered from all anticipated side effects of such therapy
  • Pts have received immunotherapy ≤2wks to starting study drug/have not recovered from side effects of such therapy
  • Pts have received investigational drugs ≤2wks to starting study drug unless they have fully recovered from all anticipated side effects of such therapy
  • Pts have received XRT ≤4wks to starting study drug unless they have fully recovered from all anticipated side effects of such therapy
  • Pts have undergone major non-CNS surgery ≤2wks to starting study drug/pts who have not recovered from side effects of such therapy
  • Cardiac pacemaker
  • Ferromagnetic metal implants other than those approved as safe for use in MR scanners
  • Claustrophobia
  • Obesity
  • Female pts who are pregnant/breast feeding/adults of reproductive potential not employing effective method of birth control
  • Known diagnosis of HIV
  • History of another primary malignancy that is currently clinically significant/currently requiring active intervention
  • Pts unwilling to/unable to comply w protocol
  • Existing intra-tumoral hemorrhage
  • Concurrent participation in another clinical trial except for supportive care/non-treatment trials
  • Other severe acute/chronic medical/psychiatric condition/lab abnormality that may increase risk associated w study participation/study drug administration/ may interfere w interpretation of study results, & in judgment of investigator would make subject inappropriate for entry into this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00611728

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United States, North Carolina
Duke University Health System
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
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Principal Investigator: David A. Reardon, MD Duke University Health System
Additional Information:
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Responsible Party: Duke University Identifier: NCT00611728    
Other Study ID Numbers: Pro00000931
First Posted: February 11, 2008    Key Record Dates
Last Update Posted: July 21, 2014
Last Verified: December 2011
Keywords provided by Duke University:
CPT 11
Sunitinib malate
Malignant Glioma
Anaplastic astrocytoma
Anaplastic oligodendroglioma
Anaplastic oligoastrocytoma
Brain tumor
Recurrent malignant glioma
Additional relevant MeSH terms:
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Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors