Trial Information

A Complementary Trial of an Immunotherapy Vaccine Against Tumor-Specific EGFRvIII

OBJECTIVES:

Primary

- To assess humoral and cellular immune responses to adjuvant PEP-3-KLH conjugate vaccine
in patients with newly diagnosed glioblastoma multiforme (GBM).

- To assess the clinical efficacy of the PEP-3-KLH conjugate vaccine, in terms of
progression-free survival, in patients with newly diagnosed GBM.

Secondary

- To determine whether patients with GBM, who are known to be at least mildly
immunosuppressed, can respond to standard and proven vaccine strategies.

- To assess for any potential toxicity to the PEP-3-KLH conjugate vaccine in patients
with newly diagnosed GBM.

OUTLINE: This is a 2-part, multicenter study. Patients are stratified according to
participating center.

- Part 1: Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive PEP-3-KLH conjugate vaccine and sargramostim (GM-CSF)
intradermally on days 1, 15, and 29 and then monthly in the absence of disease
progression or unacceptable toxicity.

- Arm II: Patients receive placebo vaccine intradermally on days 1, 15, and 29.
Patients then receive PEP-3-KLH conjugate vaccine and GM-CSF monthly in the
absence of disease progression or unacceptable toxicity.

- Part 2: Patients receive PEP-3-KLH conjugate vaccine and GM-CSF intradermally on days
1, 15, and 29 and then monthly in the absence of disease progression or unacceptable
toxicity. Alternatively, patients receive PEP-3-KLH conjugate vaccine and GM-CSF
intradermally on days 1, 8, and 15, followed 1 week later by radiotherapy 5 days a week
and oral temozolomide once daily for up to 7 weeks. Patients with no evidence of
disease progression after completion of radiotherapy then receive PEP-3-KLH conjugate
vaccine and GM-CSF intradermally monthly in the absence of disease progression or
unacceptable toxicity. Beginning approximately 4 weeks after the completion of
radiotherapy or after the fourth vaccination, all patients receive oral temozolomide on
days 1-5 or days 1-21. Treatment with temozolomide repeats every 28 days for at least 6
months.

Patients undergo delayed-type hypersensitivity (DTH) skin testing* at baseline, after the
third vaccination, and then monthly thereafter. Patients also undergo leukapheresis to
obtain sufficient peripheral blood lymphocytes for immunologic monitoring at baseline, after
the third vaccination, and then, if applicable, at the time of positive DTH response,
disease progression, or after the sixth course of post-radiotherapy temozolomide. Methods
used for immunologic monitoring include ELISPOT assays, cytotoxicity assays, fluorescence
activated cell sorting (FACS), and ELISA.

NOTE: *Patients with positive DTH skin testing, also undergo skin punch biopsies.

After completion of study therapy, patients are followed periodically.