Clinical trial NCT00611728: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2008-02-11
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Determine MTD & DLT of SU011248 + Irinotecan in pts w RMG not on EIAEDs
timeFrame: 6 months
Secondary outcomes:
measure: Demographic & baseline characteristics
timeFrame: 6 months
measure: Efficacy observations & measurements
timeFrame: 6 months
measure: Safety observations & measurements
timeFrame: 6 months
measure: PK measurements
timeFrame: 6 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
Study officials:
affiliation: Duke Health
name: David A. Reardon, MD
role: PRINCIPAL_INVESTIGATOR
References: