Ph I Dasatinib + Erlotinib in Recurrent MG

• Status: Completed
• Trial end date: 2010-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary:

To determine maximum tolerated dose & dose limiting toxicity of dasatinib when combined w erlotinib among pts w recurrent MG

Secondary:

To further evaluate safety & tolerability of dasatinib + erlotinib To evaluate pharmacokinetics of dasatinib when administered w erlotinib among recurrent MG pts who are on & not on CYP-3A enzyme inducing anti-epileptic drugs To evaluate for anti-tumor activity with this regimen in this patient population

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Duke University
• Collaborators: Bristol-Myers Squibb; Genentech, Inc.
• Treatments: Dasatinib; Erlotinib Hydrochloride

Criteria

Inclusion Criteria:

• Diagnosis of recurrent/progressive WHO grade IV MG or WHO grade III MG. Pts with prior low-grade glioma are eligible if histologic assessment demonstrates transformation to WHO grade III / IV MG

• >18 yrs

• Karnofsky Performance Status >70 percent

• Pts presenting in 1st, 2nd / 3rd relapse. Prior therapy must have included external beam XRT

• Adequate bone marrow, liver & renal function as assessed by following:

• Hemoglobin>9.0g/dl

• ANC>1,500/mm3

• Platelet count>100,000/mm3

• Total bilirubin<1.5 x ULN

• ALT & AST<2.5 x ULN

• INR<1.5 or PT/PTT within normal limits. Pts receiving anti-coagulation treatment w low-molecular weight heparin allowed to participate, oral warfarin is not permitted

• Creatinine<1.5 x ULN

• Serum Na, K+, Mg2+, Phosphate & Ca2+ >LLN

• Interval<2 wks between prior surgical resection & initiation of study regimen

• Interval <12 weeks from completion of standard, daily XRT, unless one of following occurs: new area of enhancement on MRI imaging that is outside XRT field; biopsy proven recurrent tumor; / radiographic evidence of progressive tumor on 2 consecutive scans >4 wks apart.

• Interval <4weeks from prior chemotherapy unless there is unequivocal evidence of tumor progression & pt has recovered from all anticipated toxicities from prior therapy

• Interval <4weeks from prior investigational agent unless there is unequivocal evidence of tumor progression & pt has recovered from all anticipated toxicities from prior therapy

• Signed written informed consent including HIPAA according to institutional guidelines. Signed informed consent must be obtained prior to any study specific procedures

• If sexually active, pts will take contraceptive measures for duration of treatments & for 4 weeks following discontinuation of dasatinib & Erlotinib.

• Women of childbearing potential must have negative serum or urine pregnancy test within 72 hrs prior to start of study drug administration

Exclusion Criteria:

• No prior dasatinib / oral EGFR-inhibitor therapy

• Pregnancy/breast feeding

• History of significant concurrent illness

->3 prior episodes of progressive disease

• Significant cardiac disease

• Excessive risk of bleeding as defined by stroke <6 months, history of CNS / intraocular bleed,/ septic endocarditis.

• Concurrent severe and/or uncontrolled medical disease that could compromise participation in study including any of following: pleural / pericardial effusion of any grade; uncontrolled diabetes; uncontrolled hypertension; active clinically serious infection >CTCAEv3 Gr2 requiring active intervention; history of clinically-significant bleeding diathesis or coagulopathy including platelet function disorder or acquired bleeding disorder within 1yr; impairment of GI function /GI disease that may significantly alter absorption of study regimen; ongoing or recent significant gastrointestinal bleeding

• Thrombolic or embolic events such as cerebrovascular accident including transient ischemic attacks <6 months

• Any hemorrhage/bleeding event >CTCAEv3AE Gr3 within 4wks of 1st dose of study drug

• Serious non-healing wound, ulcer, /bone fracture

• Major surgery, open biopsy /significant traumatic injury <4 weeks of 1st study drug

• Known HIV infection/chronic Hepatitis B/C

• Pt is <3yrs free of another primary malignancy except: if other primary malignancy is either not currently clinically significant/does not require active intervention. Existence of any other malignant disease is not allowed.

• Pts unwilling to/unable to comply with protocol including ability to swallow whole pills/presence of any malabsorption syndrome

• Concurrent administration of warfarin, rifampin/St. John's Wort

• Subjects w hypokalemia/hypomagnesemia if it cannot be corrected

• Prisoners/subjects who are compulsorily detained for treatment of either psychiatric/physical illness