Ph I SU011248 + Irinotecan in Treatment of Pts w MG

This study has been completed.
Information provided by (Responsible Party):
Duke University Identifier:
First received: January 29, 2008
Last updated: February 15, 2013
Last verified: December 2011

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 Intervention Phase
Drug: SU011248 & Irinotecan
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of SU011248 Plus Irinotecan in the Treatment of Patients With Malignant Glioma

Resource links provided by NLM:

Further study details as provided by Duke University:

Primary Outcome Measures:
  • Determine MTD & DLT of SU011248 + Irinotecan in pts w RMG not on EIAEDs [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Demographic & baseline characteristics [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Efficacy observations & measurements [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Safety observations & measurements [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • PK measurements [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 25
Study Start Date: March 2008
Study Completion Date: September 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
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
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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
Please refer to this study by its identifier: NCT00611728

United States, North Carolina
Duke University Health System
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Principal Investigator: David A. Reardon, MD Duke University Health System
  More Information

Additional Information:
No publications provided

Responsible Party: Duke University Identifier: NCT00611728     History of Changes
Other Study ID Numbers: Pro00000931
Study First Received: January 29, 2008
Last Updated: February 15, 2013
Health Authority: United States: Institutional Review Board

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:
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors processed this record on April 17, 2014