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Phase I Study of Dasatinib Plus Erlotinib in Recurrent Malignant Glioma

Phase 1
18 Years
Not Enrolling
Glioblastoma, Gliosarcoma

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Trial Information

Phase I Study of Dasatinib Plus Erlotinib in Recurrent Malignant Glioma

Tarceva administered on continuous oral dosing schedule at 150 mg/day for pts not on EIAEDs
& 450 mg/day for pts on EIAEDs. Starting dose level of dasatinib will be 100 mg once day via
continuous oral daily dosing. Dasatinib will be increased in successive cohorts of enrolled
pts. Pts will remain on treatment until excessive toxicity, progressive disease, withdrawal
of consent/death.

Pts have confirmed diagnosis of recurrent/progressive WHO gr IV MG / WHO grade III MG. Phase
I 3+3 dose escalation design w 2 independently escalated stratum: stratum A-pts not on
CYP3A-enzyme inducing anti-epileptic drugs; stratum B-pts on EIAEDs. Assessment of safety
will be based mainly on frequency of adverse events, particularly adverse events leading to
discontinuation of treatment & on number of significant lab abnormalities.

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

- 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

- 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

Type of Study:


Study Design:

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

Outcome Measure:

To determine MTD & DLT of Dasatinib when combined w Erlotinib among pts w Recurrent MG

Outcome Time Frame:

12 months

Safety Issue:


Principal Investigator

Annick Desjardins, MD, FRCPC

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University Health System


United States: Food and Drug Administration

Study ID:




Start Date:

January 2008

Completion Date:

July 2010

Related Keywords:

  • Glioblastoma
  • Gliosarcoma
  • Glioblastoma
  • Gliosarcoma
  • GBM
  • Recurrent MG
  • Erlotinib
  • Dasatinib
  • Brain tumor
  • Malignant glioma
  • Tarceva
  • Sprycel
  • Glioblastoma
  • Gliosarcoma
  • Glioma



Duke University Health System Durham, North Carolina  27705