CTSU N0577 - "Phase III Intergroup Study of Radiotherapy versus Temozolomide Alone versus Radiotherapy with Concomitant and Adjuvant Temozolomide for Patients with 1p/19q Codeleted Anaplastic Glioma"

NOTES: 

1)  See Neurocognitive Certification requirement in protocol (MANDATORY for 1st 50 pts).  Examiners must be certified b/f enrolling any patients.

2)  See IMRT certification requirement in protocol.

Treatment Plan    (Supplied Drug:  Temozolomide)

PRE-REGISTRATION (Central Pathology Review Submission)

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REGISTRATION / RANDOMIZATION (Central review confirmation & confirmation of 1p/19q Co-deleted status)

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Arm A

RT:  5940cGy/33fx, Days 1-5, weekly x 6 wks

Followed by 4-6 wk rest period

Arm B (see protocol for pre-tx regimen w/Pneumocystis carinii pneumonia [required])

RT:  5940cGy/33fx, Days 1-5, weekly x 6 wks

Temozolomide:  75mg/m2, PO, QD, weekly x 6 wks

Followed by 4 wk (+/- 3 days) rest period, then adjuv tx w/Temozolomide

Temozolomide:  150 or 200mg/m2*, PO, Days 1-5 (Wk 1), q 28 days x 6 cycles (option to extend to 12 cycles)

* 1st cycle of adjuv Temozolomide is given at 150mg/m2; dose escalated to 200mg/m2 in subsequent cycles in absence of toxicity.

Arm C (see protocol for pre-tx regimen w/Pneumocystis carinii pneumonia [required])

Temozolomide:  150 or 200mg/m2**, PO, Days 1-5 (Wk 1), q 28 days x 12 cycles

**  1st cycle of Temozolomide is given at 150mg/m2; dose escalated to 200mg/m2 in subsequent cycles in absence of toxicity.

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OBSERVATION UNTIL PD (q 8 wks x 18 mos from start of tx, then q 12 wks until PD)

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EVENT MONITORING (q 6 mos until death)

Eligibility

PRE-REGISTRATION

• Must submit tissue for mandatory central path review & deletion status determination (ASAP post-surgery).

REGISTRATION

• Age >18.

• New dx & <3 mos from surgical dx.

• Histol confirmation of anaplastic glioma (oligodendroglioma, mixed, or astrocytoma [WHO grade III], determined by pre-regist central path review, & tumor is also co-deleted for 1p & 19q.  NOTE:  Mixed gliomas are eligible, regardless of degree of astrocytic or oligodendrocytic predominance, as long as tumor is co-deleted for 1p & 19q.

• Surgery <2 wks pre-regist & recovered from all side effects.

• <21 days pre-regist:  ANC >1500; platelets >100,000; Hgb >9.0g/dL; total bili <1.5x UNL; SGOT <3x UNL; creat <1.5x ULN.

• Negative pregnancy test <7 days pre-regist (if applicable).

• Willing and able to complete neurocognitive exam w/o assistance & QOL by themselves or w/assistance.

• ECOG perf status 0-2.

• Willing to provide tissue for research purposes.

• No pregnant or nursing women.  Men/Women of reproductive potential must use adequate contraception.

• No prior surgery, RT, or chemo for any CNS neoplasm (hormones, vitamins, & growth factors are not considered chemo).

• No co-morbid illnesses or other severe concurrent disease to preclude study participation & asmt of regimens (investigator's judgement).

• No concomitant serious immuno-compromised status (other than that related to concomitant steroids).

• No active uncontrolled systemic infection or HIV.

• Must not be receiving any other investigational agent that would be considered a tx for the prim neoplasm.

• No other active malignancy except non-melanoma skin cancer or in situ cervical carcinoma.  NOTE:  If there is a prior malignancy, must not be receiving other specific tx (other than hormonal) for their cancer.

• No prior MI w/i past 6 mos or CHF requiring ongoing maintenance therapy for life-threatening ventricular arrhythmias.

• No recent hepatitis infection or significant risk for reactivation of hepatitis (treating physician's judgement).

• PRESTUDY REQUIREMENTS:

  • Path review & determination of deletion status*#@

  • RO consult*

  • H&P, wt, perf status, ht**

  • Neuro hx & exam**

  • Pregnancy test (if applicable, w/i 7 days pre-regist)

  • ANC, platelets, Hgb**

  • SGOT, alk phos, total bili, creat, calcium, phos, glucose, sodium, potassium**

  • Head MRI w/contrast or CT w/contrast (MRI preferred unless contraindications)**

  • Recording of steroid dose**

  • Optional research blood draw (collect post-regist, but b/f any tx)***

  • Mandatory research tissue$

  • Neurocognitive/QOL questionnaire booklets (Mandatory for 1st 50 pts)**

  *      Pre-regist

  **   <21 days pre-regist

  ***  For banking.  EDTA & Na heparin blood & EDTA plasma.  Contact KCCOP for kit.

  #     Allow 10 business days from time NCCTG receives ALL path materials & usable tissue to obtain deletion status & communicate to site.

  @  Submit ASAP post-surg & prior to enrollment (pre-regist requirement for central review & deletion status):  1)  All diagnostic slides; & 2) FFPE tissue blocks w/corresponding H&E (or 5 unstained slides w/1 corresponding H&E).  Send to:  NCCTG Operations Office; PC Office (Study N0577); Rochester, MN.

  $     Submit <30 days post-regist (correlative studies):  1)  All diagnostic slides; 2) FFPE tissue blocks w/corresponding H&E (or 5 unstained slides w/1 corresponding H&E); & 3) 15 unstained slides w/2 corresponding H&Es.  NOTE:  If FFPE tissue block was previously submitted for determination of deletion status, no additional tissue slides are required.  These slides are required if unstained slides (instead of a tissue block) were originally submitted for the pre-regist requirement for determination of deletion status.

• Signed informed consent.