MDA 2004-0662 - "A Randomized, Factorial-Design, Phase II Trial of Temozolomide Alone and in Combination With Possible Permutations of Thalidomide, Isotretinoin, and/or Celecoxib as Post-Radiation Adjuvant Therapy of Glioblastoma Multiforme"

Treatment Plan    (Supplied Drug:  Temozolomide)

After completion of RT and w/i 5 wks of last RT dose, pts who have not had PD will be randomized to one of following:

Arm

1          Temozolomide Alone

2          Temozolomide + Thalidomide

3          Temozolomide + Isotretinoin

4          Temozolomide + Celecoxib

5          Temozolomide + Thalidomide/Isotretinoin

6          Temozolomide + Thalidomide/Celecoxib

7          Temozolomide + Isotretinoin/Celecoxib

8          Temozolomide + Thalidomide/Isotretinoin/Celecoxib

Temozolomide:  150mg/m2, PO, q HS, 7 days on / 7 days off

Thalidomide:  400mg, PO, QD, continuous dosing

Isotretinoin:  80mg/m2, PO, BID (divided dosing - total 80mg/m2/day), Days 1-21 of 28 day cycle (each BID dose rounded up to next 10mg level)

Celecoxib:  400mg, PO, BID, continuous dosing

Eligibility

• Histol-proven supratentorial glioblastoma multiforme.  Must have had either bx, subtotal, or gross total resection of tumor.

• Must have completed post-op or post-bx RT (concurrent Temozolomide during RT is allowed & recommended).  No other concurrent chemo is allowed.

• Regist and randomiz occurs after completion, but no later than 5 wks after, RT.

• Age >18.

• Karnofsky PS >60 at enrollment.

• Within 14 days pre-enrollment:   ANC >1500/mm3, platelets >100,000/mm3, SGOT & alk phos <2x ULN, bili <1.5mg, BUN & creat <1.5x instit normal.

• Post-op GD-DPTA MRI after RT & w/i 14 days pre-enrollment.

• No hx of any other cancer (except non-melanoma skin or in situ  cervical), unless in CR and off all therapy for >3 yrs.

• Must use effective contraception.

• No active infection.

• No disease to obscure toxicity or dangerously alter drug metabolism.

• No serious intercurrent medical illness.

• No documented hx of peptic ulcer disease or hx of active/recent GI bleeding (w/i last 3 mos).

• No hx of allergic reactions to compounds of similar chemical or biologic compostion to Celecoxib or sulfonamides.  No pts experiencing asthma, urticaria, or allergic reactions to aspirin or other NSAIDs.

• No pregnant or nursing women.

• PRESTUDY REQUIREMENTS (Within 7 days pre-intiation of study drug, unless otherwise specified):

  • Demographics, medical hx, ht

  • PE (w/neuro exam)*

  • Wt, VS*

  • Karnofsky PS*

  • Adverse events

  • CBC/diff/platelets*

  • PT, INR* (pts receiving Thalidomide only)

  • SMA-12*

  • Cholesterol, triglycerides* (pts receiving Isotretinoin only)

  • Anticonvulsant levels

  • CrCl

  • Pregnancy test (if applicable, w/i 24 hrs of beginning Thalidomide)

  • Tumor msmt (MRI)*

  • Concomitant meds

  *     Within 14 days pre-regist

• Signed informed consent.