Ph I SU011248 + Irinotecan in Treatment of Pts w MG

NCT ID: NCT00611728

Last Updated: 2014-07-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2010-09-30

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.

Conditions

Glioblastoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

SU011248-Sutent-Sunitinib; Irinotecan-CPT 11-Camptosar

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David A. Reardon, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Health

Locations

Duke University Health System

Durham, North Carolina, United States

Countries

United States

Related Links

http://www.cancer.duke.edu/btc/

The Preston Robert Tisch Brain Tumor Center at DUKE

Other Identifiers

Pro00000931

Identifier Type: -

Identifier Source: org_study_id