Thema: Studie: PS 341 in the Treatment of Recurrent Gliomas
Studie: PS 341 in the Treatment of Recurrent Gliomas
Jörg[a]
07.10.2003 23:07:52
Clinical Trial - NABTT 9910
Phase I Evaluation of the Safety of PS 341 in the Treatment of
Recurrent Gliomas
Objectives: Phase I - To determine the maximum tolerated dose (MTD).
Patient Population: Patients with recurrent anaplastic glioma (Anaplastic Astrocytoma, Anaplastic oligodendroglioma or Glioblastoma Multiforme), which is progressive or recurrent following treatment with radiation therapy with or without previous chemotherapy.
Drug Rationale: PS 341 is a proteasome inhibitor. Proteasome inhibitors act through multiple mechanisms to arrest tumor growth, tumor spread and angiogenesis. PS341 is a proteasome inhibitor that blocks cell division. We hope it will slow tumor growth and the spread of tumor cells by blocking the proteins that help control cell growth.
Stratification: Certain antiepileptic drugs induce cytochrome P450 enzymatic activity and may result in enhanced hepatic metabolism of chemotherapeutic agents with a substantial reduction of plasma levels. Based on this observation, we will stratify patients based on their P450 status as (Group A) or not receiving (Group B) anticonvulsants that are metabolized by the P450 hepatic enzyme complex. These dose escalations will proceed separately. A list of commonly used drugs is attached.
Administration: PS 341 is given by rapid IV push (over 3-5 seconds) a peripheral line.
Schedule: PS 341 is given on a once a day, twice a week regimen for four weeks, followed by two weeks of rest. Each cycle is six weeks in length. Patients must be treated on a Monday and Thursday or Tuesday and Friday dosing schedule. Patients will have an MRI following two cycles (12 weeks) to evaluate response to treatment, if stable or improved the patient will continue for two more cycles.
Possible Side Effects:
Neutropenia
Thrombocytopenia
Anemia
Fever, Fatigue (lethargy, malaise, asthenia)
norexia, diarrhea, nausea, vomiting
Hypotension, rash
Hyponatremia
Sensory neuropathy
Patient Monitoring:
Heme 8 and anti-convulsant levels weekly
H&P, Neuro Exam, Toxicity Evaluation, Metabolic panel -every 6 weeks
H&P, Neuro Exam, Toxicity Evaluation, MRI and Comprehensive panel-every 12 weeks
Resource Utilization: It is anticipated that patients will be selected from the patient population at the Emory Clinic and Emory University Hospital.
Winship Cancer Institute of Emory University
1365 Clifton Road, N.E. Building C
Atlanta, GA 30322 - (404) 778-5180, (404) 778-5016 - Fax
Phase I Evaluation of the Safety of PS 341 in the Treatment of
Recurrent Gliomas
Objectives: Phase I - To determine the maximum tolerated dose (MTD).
Patient Population: Patients with recurrent anaplastic glioma (Anaplastic Astrocytoma, Anaplastic oligodendroglioma or Glioblastoma Multiforme), which is progressive or recurrent following treatment with radiation therapy with or without previous chemotherapy.
Drug Rationale: PS 341 is a proteasome inhibitor. Proteasome inhibitors act through multiple mechanisms to arrest tumor growth, tumor spread and angiogenesis. PS341 is a proteasome inhibitor that blocks cell division. We hope it will slow tumor growth and the spread of tumor cells by blocking the proteins that help control cell growth.
Stratification: Certain antiepileptic drugs induce cytochrome P450 enzymatic activity and may result in enhanced hepatic metabolism of chemotherapeutic agents with a substantial reduction of plasma levels. Based on this observation, we will stratify patients based on their P450 status as (Group A) or not receiving (Group B) anticonvulsants that are metabolized by the P450 hepatic enzyme complex. These dose escalations will proceed separately. A list of commonly used drugs is attached.
Administration: PS 341 is given by rapid IV push (over 3-5 seconds) a peripheral line.
Schedule: PS 341 is given on a once a day, twice a week regimen for four weeks, followed by two weeks of rest. Each cycle is six weeks in length. Patients must be treated on a Monday and Thursday or Tuesday and Friday dosing schedule. Patients will have an MRI following two cycles (12 weeks) to evaluate response to treatment, if stable or improved the patient will continue for two more cycles.
Possible Side Effects:
Neutropenia
Thrombocytopenia
Anemia
Fever, Fatigue (lethargy, malaise, asthenia)
norexia, diarrhea, nausea, vomiting
Hypotension, rash
Hyponatremia
Sensory neuropathy
Patient Monitoring:
Heme 8 and anti-convulsant levels weekly
H&P, Neuro Exam, Toxicity Evaluation, Metabolic panel -every 6 weeks
H&P, Neuro Exam, Toxicity Evaluation, MRI and Comprehensive panel-every 12 weeks
Resource Utilization: It is anticipated that patients will be selected from the patient population at the Emory Clinic and Emory University Hospital.
Winship Cancer Institute of Emory University
1365 Clifton Road, N.E. Building C
Atlanta, GA 30322 - (404) 778-5180, (404) 778-5016 - Fax
Jörg[a]
