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Biotech / Medical : Procept (PRCT): 50% rise on high volume. Why? -- Ignore unavailable to you. Want to Upgrade?

To: Douglas who wrote (407)	6/21/1999 8:21:00 AM
From: Douglas	Respond to of 455

Phase I Study of Carmustine Plus O6-Benzylguanine in Patients with Recurrent, Persistent, or Progressive Cerebral Anaplastic Gliomas Protocol IDs: DUMC-980-98-6R4, NCI-T94-0080, DUMC-929-97-6R3 Protocol Type: treatment Sponsorship: NCI-sponsored, NCI CTEP-approved Status: Active Age Range: 18 and over PROJECTED ACCRUAL: A total of 24-56 patients (12-28 per stratum) will be accrued in 12 months. OBJECTIVES: I. Determine the maximum tolerated dose of carmustine when administered following O6-benzylguanine in patients with recurrent, persistent, or progressive cerebral anaplastic gliomas. II. Characterize the toxic effects associated with this treatment regimen in these patients. III. Observe patients for clinical antitumor response when treated with this regimen. PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- Histologically proven recurrent, persistent, or progressive glioblastoma multiforme or anaplastic astrocytoma diagnosed by biopsy/resection Evaluable residual disease by MRI or CT scan --Prior/Concurrent Therapy-- Biologic therapy: Not specified Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks since prior nitrosourea, procarbazine, or mitomycin) and recovered Endocrine therapy: Concurrent corticosteroid therapy must be stable for at least 1 week prior to study, if clinically possible Radiotherapy: At least 4 weeks since prior radiotherapy and recovered Surgery: Not specified --Patient Characteristics-- Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: Absolute granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: SGOT no greater than 2.5 times upper limit of normal Bilirubin within normal limits Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance greater than 60 mL/min BUN no greater than 25 mg/dL Pulmonary: DLCO greater than 80% predicted Other: Not pregnant or nursing Fertile patients must use effective contraceptive method during and for 2 months after study PROTOCOL OUTLINE: Patients are stratified according to prior nitrosourea administration (yes or no). An initial cohort of 3 patients per stratum is treated with intravenous O6-benzylguanine followed approximately 1 hour later by intravenous carmustine every 6 weeks. Additional cohorts of 3-6 patients are treated with escalating doses of carmustine until dose limiting toxicity (DLT) is observed. The maximum tolerated dose is defined as the dose at which no more than 1 of 6 patients experiences DLT. Courses are repeated every 6 weeks in the absence of disease progression or unacceptable toxicity. WARNING: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening for or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. PARTICIPATING ORGANIZATIONS/INVESTIGATORS Henry S. Friedman, Chair, Ph: 919-684-5301 Duke Comprehensive Cancer Center

To: Douglas who wrote (407)	6/21/1999 8:23:00 AM
From: Douglas	Respond to of 455

Phase I Study of Presurgical O6-Benzylguanine in the Treatment of Patients With Malignant Glioma Protocol IDs: NABTC-9702, NCI-T96-0103 Protocol Type: treatment Sponsorship: NCI-sponsored, NCI CTEP-approved Status: Active Age Range: 18 and over PROJECTED ACCRUAL: A minimum of 14 patients will be accrued with about 3 patients per month. OBJECTIVES: I. Define the dose of O6-benzylguanine (O6-BG) that produces total depletion of tumor O6-alkylguanine-DNA alkyltransferase (AGT) levels in more than 90% of cases of cerebral anaplastic astrocytoma or glioblastoma multiforme. II. Evaluate the qualitative and quantitative toxicities of O6-BG in this patient population. PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- Must be undergoing a diagnostic/therapeutic craniotomy for biopsy/resection of recurrent or newly diagnosed (or presumed) cerebral anaplastic astrocytoma or glioblastoma multiforme Patients undergoing stereotactic biopsy or partial resectioning are eligible --Prior/Concurrent Therapy-- No concurrent therapy for any other malignancy At least 2 weeks since any other investigational drug Biologic therapy: Not specified Chemotherapy: Must have failed or received no prior treatment with a nitrosourea, procarbazine, or temozolomide No prior O6-BG At least 4 weeks since chemotherapy and recovered from all toxic effects Endocrine therapy: Not specified Radiotherapy: At least 6 weeks since radiotherapy No more than 10-20% of bone marrow should have had received radiotherapy --Patient Characteristics-- Age: 18 and over Performance status: SWOG 0-2 OR Karnofsky 60-100% Hematopoietic: WBC at least 3,500/mm3 Absolute neutrophil count at least 1,800/mm3 Platelet count at least 125,000/mm3 Hemoglobin at least 9 g/dL Hepatic: Bilirubin less than 1.5 mg/dL SGOT less than 2 times upper limits of normal Renal: Creatinine less than 1.5 mg/dL OR Creatinine clearance greater than 70 mL/min Cardiovascular: No severe cardiac disease such as uncontrolled arrhythmias or conduction defects No coronary artery disease Other: No other medical illnesses that would compromise patient's ability to tolerate this therapy such as: Major problems with edema Poorly controlled hypertension (greater than 180 mmHg systolic, greater than 110 mmHg diastolic) Major psychiatric illness No other malignancy requiring active therapy Not pregnant or nursing Adequate contraception required of all fertile patients PROTOCOL OUTLINE: This is a dose escalating study in which patients are stratified by disease status (newly diagnosed vs recurrent disease), prior chemotherapy (yes vs no) and concurrent anticonvulsants (yes vs no). A single dose of O6-benzylguanine (06-BG) is administered intravenously to the first 10 patients over 1 hour, 6 hours prior to surgical intervention. Dosage escalation and accrual depend on toleration of treatment. If at least 3 of 10 patients have 06-alkylguanine-DNA alkyltransferase (AGT) levels that are detectable, that dose is escalated and 10 additional patients are treated. Dose escalation continues until at least 8 of 10 patient have undetectable enzyme activity. At this point 4 more patients are accrued. If at least 11 of 14 patients at this dose have undetectable AGT levels, then this dose constitutes the biologic modulatory dose of O6-BG. If there are fewer than 11 of 14 patients with undetectable AGT levels, the accrual continues with 10 patients at a higher dose and so on until at least 11 of 14 patients give undetectable AGT levels. Treatment ends short of completion if there is unacceptable toxicity following O6-BG that delays surgery for more than 24 hours, or if the removal of the tumor specimen occurs less than 3 hours or more than 9 hours after the completion of the O6-BG infusion. WARNING: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening for or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. PARTICIPATING ORGANIZATIONS/INVESTIGATORS Michael Del Prados, Chair, Ph: 415-476-2966 North American Brain Tumor Consortium

To: Douglas who wrote (407)	6/21/1999 8:25:00 AM
From: Douglas	Read Replies (1) \| Respond to of 455

Phase I Study of O6-Benzylguanine plus Carmustine for Advanced Melanoma, Breast Cancer, Colorectal Cancer, Lymphoma, Gliomas, and Other Adult Solid Tumors Protocol IDs: UCCRC-7341, NCI-T94-0082C Protocol Type: treatment Sponsorship: NCI-sponsored, NCI CTEP-approved Status: Active Age Range: 18 and over PROJECTED ACCRUAL: 3-6 patients will be entered at each dose studied. OBJECTIVES: I. Define the maximum tolerated dose and associated acute and chronic toxic effects of O6-benzylguanine (BG) administered alone and in combination with carmustine (BCNU). II. Define the maximum tolerated dose and associated acute and chronic toxic effects of BCNU administered alone and in combination with BG. III. Describe the distribution, metabolism, and elimination of BG in humans. IV. Determine the dose of BG required to achieve at least a 90% depletion of O6-alkylguanine-DNA alkyltransferase (AGT) activity in human lymphocytes and tumor tissue. V. Assess the time to recovery of AGT activity following administration of BG. VI. Define the relationships between BG pharmacokinetics and the extent and duration of depletion of AGT activity. VII. Determine the frequency of GGA to AGA mutation at codon 160 in exon 5 of the human AGT gene in cancer patients receiving BG and to correlate with in vivo sensitivity to BG. PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- Any histologically confirmed advanced cancer for which one of the following applies: Refractory to standard therapy No standard therapy exists Protocol treatment is an acceptable alternative to standard therapy The following histologies are included: Melanoma Breast cancer Colorectal cancer Lymphoma Malignant gliomas Measurable or evaluable disease required No bone marrow metastases No CNS metastases requiring therapy Brain CT required within 2 weeks of entry for melanoma patients Previously treated, stable metastases eligible --Prior/Concurrent Therapy-- Recovery from prior therapy required Biologic therapy: At least 4 weeks since immunotherapy Chemotherapy: At least 4 weeks since chemotherapy (6 weeks since mitomycin or nitrosoureas) Endocrine therapy: Stable steroid dose for at least 2 weeks prior to entry required of brain tumor patients Radiotherapy: At least 4 weeks since radiotherapy Surgery: Not specified --Patient Characteristics-- Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: At least 8 weeks Hematopoietic: WBC at least 3,500/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 10 g/dL Hepatic: Bilirubin no more than 1.6 mg/dL AST less than 2 times normal Renal: Creatinine no more than 1.6 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: No significant cardiac disorder that would compromise treatment or obscure results Other: No active infection No significant neurologic, endocrine, gastrointestinal, rheumatologic, dermatologic, or allergic disorder that would compromise treatment or obscure results No serious medical or psychiatric illness that would prevent informed consent or treatment No pregnant women Adequate contraception required of fertile patients during and for 2 months after completion of treatment Laboratory studies required to determine eligibility within 1 week of entry; pulmonary function studies, imaging for tumor assessment, and other pretreatment studies required within 2 weeks of entry PROTOCOL OUTLINE: All patients receive O6-benzylguanine as a single dose. Two weeks later, patients receive a second dose, followed 1 hour later by carmustine. Groups of 2-6 patients are treated at increasing doses of O6-benzylguanine until the optimum dose is determined; the dose of carmustine is then increased in additional patient groups to determine its maximum tolerated dose. Courses of O6-benzylguanine/carmustine then repeat every 6 weeks until disease progression. Treatment continues until disease progression, at which time patients may be eligible for further treatment at the next higher dose. WARNING: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening for or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. PARTICIPATING ORGANIZATIONS/INVESTIGATORS Richard L. Schilsky, Chair, Ph: 773-702-6180 University of Chicago Cancer Research Center