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Ph I SU011248 + Irinotecan in Treatment of Pts w MG

Information source: Duke University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Glioblastoma

Intervention: SU011248 & Irinotecan (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Duke University

Official(s) and/or principal investigator(s):
David A. Reardon, MD, Principal Investigator, Affiliation: Duke University Health System

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

Clinical Details

Official title: A Phase I Study of SU011248 Plus Irinotecan in the Treatment of Patients With Malignant Glioma

Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

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

Secondary outcome:

Demographic & baseline characteristics

Efficacy observations & measurements

Safety observations & measurements

PK measurements

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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

Duke University Health System, Durham, North Carolina 27710, United States
Additional Information

The Preston Robert Tisch Brain Tumor Center at DUKE

Starting date: March 2008
Last updated: July 18, 2014

Page last updated: August 23, 2015

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