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Ph I SU011248 + Irinotecan in Treatment of Pts w MG

Primary Purpose

Glioblastoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SU011248 & Irinotecan
Sponsored by
Duke University
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring Glioblastoma, CPT 11, Sutent, Sunitinib, Sunitinib malate, Malignant Glioma, GBM, Irinotecan, Camptosar, Anaplastic astrocytoma, Anaplastic oligodendroglioma, Anaplastic oligoastrocytoma, SU011248, Brain tumor, Recurrent malignant glioma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Duke University Health System

Outcomes

Primary Outcome Measures

Determine MTD & DLT of SU011248 + Irinotecan in pts w RMG not on EIAEDs

Secondary Outcome Measures

Demographic & baseline characteristics
Efficacy observations & measurements
Safety observations & measurements
PK measurements

Full Information

First Posted
January 29, 2008
Last Updated
July 18, 2014
Sponsor
Duke University
Collaborators
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT00611728
Brief Title
Ph I SU011248 + Irinotecan in Treatment of Pts w MG
Official Title
A Phase I Study of SU011248 Plus Irinotecan in the Treatment of Patients With Malignant Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2011
Overall Recruitment Status
Completed
Study Start Date
March 2008 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
September 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma
Keywords
Glioblastoma, CPT 11, Sutent, Sunitinib, Sunitinib malate, Malignant Glioma, GBM, Irinotecan, Camptosar, Anaplastic astrocytoma, Anaplastic oligodendroglioma, Anaplastic oligoastrocytoma, SU011248, Brain tumor, Recurrent malignant glioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
SU011248 & Irinotecan
Other Intervention Name(s)
SU011248-Sutent-Sunitinib, Irinotecan-CPT 11-Camptosar
Intervention Description
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.
Primary Outcome Measure Information:
Title
Determine MTD & DLT of SU011248 + Irinotecan in pts w RMG not on EIAEDs
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Demographic & baseline characteristics
Time Frame
6 months
Title
Efficacy observations & measurements
Time Frame
6 months
Title
Safety observations & measurements
Time Frame
6 months
Title
PK measurements
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David A. Reardon, MD
Organizational Affiliation
Duke Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Health System
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.cancer.duke.edu/btc/
Description
The Preston Robert Tisch Brain Tumor Center at DUKE

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Ph I SU011248 + Irinotecan in Treatment of Pts w MG

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