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RTOG 0627 - "Phase II Trial of Dasatinib in Patients with Recurrent Glioblastoma Multiforme"
Treatment Plan (Supplied Drug: Dasatinib)
Dasatinib: 100mg, PO, BID (see protocol for intrapatient dose escalation scheudule)
Continue q 28 days until disease progression or adverse events.
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CT or MRI q 2 mos
Eligibility
Histol-proven GBM. Gliosarcoma is also allowed.
Must consent to tissue submission for central path review (except pts who have already undergone central path review for another RTOG GBM trial).
Must consent to molecular analysis of pre-Dasatinib tumor tissue. Must have tumors overexpressing >2 known dasatinib targets (SRC, KIT, PDGFR, & EPHA2).
H&P, ht, wt w/i 10 days pre-regist.
Brain MRI w/ & w/o gadolinium w/i 10 days pre-regist. Contrast-enhanced CT allowed if pt cannot undergo MRI.
KPS >60.
Age >18.
Within 10 days pre-regist: ANC >1000 cells/mm3, platelets >75,000 cells/mm3, Hgb >8.0 g/dl (transfusion or other intervention is acceptable), Leukocytes >3000 cells/mm3, ALC >500 cells/mm3, total bili <1.5x IULN, SGOT/SGPT <2.5x IULN, creat <3x IULN or CrCl >60 mL/min/1.73m2 (for pts w/creat levels above instit norm).
Must have undergone prior tx w/RT and Temozolomide. No other prior txs allowed.
Unequivocal MRI or CT evidence for tumor progression (use same type of scan throughout tx). Must be on stable or decreasing dose of corticosteroids >5 days b/f baseline MRI/CT.
Must have recovered from effects of any prior surgery for recur/progres disease. Prim endpoint is progression-free survival after 6 mos of tx (therefore pts who recently had resection w/o meas disease post-op are also eligible). Meas disease is not required for eligibility in pts who recently underwent resection if the following are met:
Progression of disease led to surgery
Gliadel wafers were not placed during most recent surgery
Neither convection enhanced delivery nor catheters for infusion of chemo were used during most recent surgery
Radioactive seeds were not placed during most recent surgery
Histol of most recent surgery documented recur/persis/prog malignant glioma
Women of childbearing potential must have negative b-HCG pregnancy test <3 days pre-regist.
No prior invasive malignancy (except non-melanoma skin cancer) unless disease-free >3 yrs. Carcinoma in situ of breast, oral cavity, or cervix are all allowed.
No RT w/i 4 wks or Temozolomide w/i 14 days pre-regist or failure to recover from their adverse events.
No use of other investigational agents.
No severe, active cormobidity, defined as:
Any clinically significant cardiovascular disease
Acute bacterial or fungal infection requiring IV antibiotics at regist
COPD exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at regist
AIDS based on current CDC definition (HIV testing is not required for study entry)
No pregnant or nursing women, or men/women of childbearing potential who are unwilling to use effective contraception.
No allergic reactions to compounds of similar chemical or biologic composition to Dasatinib.
No concurrent tx w/any meds or substances that are potent inhibitors or inducers of CYP3A4.
No use of hepatic enzyme inducing antiepileptic drugs (EIAEDs). If previously taking EIAEDs, must have been discontinued >2 wks pre-Dasatinib initiation.
Pts requiring antacids should use short-acting, locally active agents (e.g., Maalox, Mylanta). These agents should not be taken 2 hrs b/f or 2 hrs after Dasatinib.
No use of antithrombotic &/or antiplatelet agents.
No use of Ibuprofen & other NSAIDs.
No condition resulting in inability to swallow and retain Dasatinib tablets.
No prior tx w/stereotactic radiosurgery (including Gamma-Knife, Cyberknife, or other variants) or brachytherapy.
PRESTUDY REQUIREMENTS:
H&P, concurrent meds, VS, ht, wt, PS
CBC/diff/platelets
Chem profile (to include lytes), LDH
EKG (as indicated)
Radiologic eval
b-HCG (if applicable)
Tissue submission (post-regist/pre-tx) - MANDATORY if not enrolled in an RTOG GBM trial mandating central review
Signed informed consent.