Clinical Trials/Studies

Clinical Trials for Adults | H9H-MC-JBAI, Phase 1b/2a Study Combining LY2157299 with Standard Temozolomide-based Radiochemotherapy in Patients with Newly Diagnosed Malignant Glioma

Purpose
Phase 1b:
To determine the safe and tolerable Phase 2 dose of LY2157299 in combination with radiochemotherapy with TMZ in patients with glioma.

Phase 2a:
To confirm the tolerability and evaluate the pharmacodynamic effect of LY2157299 in combination with chemo-radiation in patients with newly diagnosed glioblastoma (as measured by changes in response biomarkers and their relationship to clinical benefit [e.g. 12-month OS rate])

Eligibility Criteria:

• Phase 1b newly diagnosed WHO gr. 3 & 4 (2 cohorts to eval DLT before Phase 2a is open)
• Phase 2a newly diagnosed Who gr. 4 only
• Biopsy or Resection no more than 6 wks prior to txt and tissue available from surgery
• MRI w/in 72hrs after surgery
• No prior XRT, cytotoxic or non cytotoxic txt, Gliadel wafers
• ECOG 0-1/KPS > 70%
• No moderate or severe cardiac disease
• Cardiac ejection fraction w/in institutional range of normal as measured by Echo w/ Doppler
• No history of any other cancer within 3yrs (except non-melanoma skin cancer or carcinoma in situ of cervix)
• No Stereotactic radiosurgery/Gamma-Knife/Brachytherapy
• Labs within 14 days prior to registration: (Hgb level may be reached by transfusion)
  • WBC >  3.0
  • ANC >  1500
  • Plts >  100,000
  • Hbg > 10
  • Alk Phos, AST, ALT <  2.5 x ULN
  • Bili <  2.0 x ULN
  • Creatinine < 1.5

Treatment Plan:

• Phase 1 is in Cohort 2 with dose of 150mg BID
• Phase 2 is randomized and dose will be based on Phase 1 findings (approx. 14pts control arm)
• LY2157299 concomitantly with TMZ and RTX followed by adjuvant LY2157299 and TMZ
• Both medications are to be taken on an empty stomach (2hrs before or 2hrs after a meal)
• LY2157299 is an oral medication and should be take prior to TMZ and XRT (LY2157299 15-30min before TMZ)
• LY2157299 will be taken 14 days on/14 days off morning and evening, dose depends on Phase and Cohort
• TMZ will be taken daily during radiation starting morning before first dose of XRT. 28days after XRT begin 5 day TMZ which will be taken during the off time of LY2157299
• One cycle is defined as 28 days (6 wks of radiation = cycle 1 and half of cycle 2)
• Patients Must have XRT at Duke and be able to travel or stay. Multiple PK’s and Blood draws are required along with ECG’s
• Treatments Should Start on a Tuesday or Wednesday