Gene Therapy in Treating Patients With Recurrent or Progressive Brain Tumors
Gene Therapy in Treating Patients With Recurrent or Progressive Brain Tumors
RATIONALE: Inserting the gene for p53 into a person's brain cells may improve the body's
 ability to fight cancer.

 PURPOSE: Phase I trial to study the effectiveness of p53 gene therapy with SCH-58500 in
 treating patients who have recurrent, or progressive glioblastoma multiforme, anaplastic
 astrocytoma, or anaplastic mixed glioma that can be removed during surgery.
OBJECTIVES: I. Estimate the efficiency of tumor cell transduction with adenovirus p53
 delivered stereotactically to patients with recurrent or progressive resectable glioblastoma
 multiforme, anaplastic astrocytoma, or anaplastic mixed glioma. II. Determine the maximum
 tolerated dose of adenovirus p53 delivered stereotactically and with craniotomy in these
 patients. III. Correlate analysis of predelivery tumor specimen p53 gene status with
 postdelivery p53 gene status, clinical status, and tumor staging in these patients treated
 with this regimen. IV. Correlate analysis of postdelivery tumor specimen p53 gene status and
 local tumor immune response with postdelivery clinical status and tumor imaging in these
 patients treated with this regimen.

 OUTLINE: This is a dose escalation, multicenter study. Patients receive SCH-58500 via
 stereotactic injection into the tumor, followed 24-72 hours later by craniotomy. Patients
 undergo tumor resection, followed by injection of SCH-58500 into the tumor bed during
 craniotomy. Cohorts of 3-6 patients receive escalating doses of SCH-58500 until the maximum
 tolerated dose (MTD) is determined. The MTD is defined as the dose immediately preceding that
 at which 3 of 3-6 patients experience dose limiting toxicity. Patients are followed at day
 28, then every 2 months for 1 year, and then annually thereafter, until another therapy is
 begun or disease progression is documented.

 PROJECTED ACCRUAL: A total of 21-42 patients will be accrued for this study over 14-27
 months.
DISEASE CHARACTERISTICS: Histologically proven glioblastoma multiforme, anaplastic
 astrocytoma, or anaplastic mixed glioma Progressive or recurrent disease following
 radiotherapy (54-64 Gy) and/or chemotherapy Tumor recurrence must have anatomic
 characteristics that allow safe and reasonable surgical intervention Measurable disease by
 serial MR or CT imaging No Li-Fraumeni syndrome or known germline defect in p53 gene No
 radiographically or surgically proven gliomatosis cerebri No tumors requiring immediate
 excision due to impending neurologic decline

 PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life
 expectancy: Not specified Hematopoietic: WBC at least 3,000/mm3 Absolute neutrophil count
 at least 1,000/mm3 Platelet count at least 100,000/mm3 Hematocrit at least 25% Hepatic:
 Bilirubin less than 1.5 mg/dL SGOT and SGPT less than 2.5 times upper limit of normal (ULN)
 PT or PTT no greater than ULN Renal: Creatinine no greater than 1.7 mg/dL Cardiovascular:
 No uncontrolled hypertension No uncontrolled or unstable angina pectoris No uncontrolled
 cardiac dysrhythmia Other: Not pregnant or nursing Negative pregnancy test Fertile patients
 must use effective contraception during and for 6 months after study HIV negative No other
 active malignancy within the past 5 years except curatively treated basal or squamous cell
 skin cancer or carcinoma in situ of the cervix No uncontrolled or serious concurrent
 infection or other serious medical illness that would preclude study therapy No viral
 syndrome diagnosed within 2 weeks prior to study No other underlying medical condition that
 would increase risk of study or obscure interpretation of adverse results No active
 adenoviral infection

 PRIOR CONCURRENT THERAPY: Biologic therapy: At least 3 weeks since prior biologic therapy
 and recovered No concurrent biologic therapy Chemotherapy: See Disease Characteristics No
 more than 1 prior chemotherapy regimen At least 3 weeks since prior chemotherapy (6 weeks
 for nitrosoureas) and recovered No prior interstitial chemotherapy such as Gliadel wafer
 implantation for present brain tumor No concurrent chemotherapy Endocrine therapy: At least
 3 weeks since prior hormonal therapy and recovered No concurrent hormonal therapy
 Radiotherapy: See Disease Characteristics No prior brachytherapy for present brain tumor At
 least 3 months since other prior radiotherapy and recovered No concurrent radiotherapy
 Surgery: See Disease Characteristics No prior radiosurgery for present brain tumor At least
 3 weeks since other prior oncologic surgery No other concurrent oncologic surgery Other: No
 other concurrent investigational drugs