COL-3 in Treating Patients With Progressive or Recurrent Brain Tumors

Study Overview
=================
Brief Summary
-----------------
RATIONALE: COL-3 may stop the growth of brain tumors by stopping blood flow to the tumor. PURPOSE: Phase I/II trial to study the effectiveness of COL-3 in treating patients who have progressive or recurrent brain tumors following radiation therapy or chemotherapy.

Detailed Description
-----------------
OBJECTIVES: Determine the maximum tolerated dose, dose limiting toxicity, and safety profile of oral COL-3 alone or when combined with anticonvulsants known to be metabolized by CYP450 in patients with progressive or recurrent high grade anaplastic astrocytoma, anaplastic oligodendroglioma, or glioblastoma multiforme. Define the pharmacokinetics and pharmacodynamics of COL-3 on this schedule and determine the effects of hepatic enzyme inducing drugs, such as anticonvulsants, on the pharmacokinetics. Determine the response rate, disease free survival, and survival in patients treated with this regimen. OUTLINE: This is a dose-escalation, multicenter study of COL-3. Patients are stratified by anticonvulsant (anticonvulsants that cause induction of CYP450 vs anticonvulsants that cause modest or no induction of CYP450 or no anticonvulsant). Phase I: Patients receive oral COL-3 daily. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of COL-3 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity. Phase II: Patients receive oral COL-3 daily at the MTD from the phase I portion of this study. Patients are followed every 2 months until death. PROJECTED ACCRUAL: A total of 15-18 patients will be accrued for phase I of the study and a total of 35 patients will be accrued for phase II of the study at a rate of 3 patients per month.

Official Title
-----------------
A Phase I/II Study of Col-3 Administered on a Continuous Daily Oral Schedule in Patients With Recurrent High-Grade Astrocytoma

Conditions
-----------------
Brain and Central Nervous System Tumors

Intervention / Treatment
-----------------
* Drug: incyclinide


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically proven high grade glioma that is progressive or recurrent following radiotherapy or chemotherapy Anaplastic astrocytoma Anaplastic oligodendroglioma Glioblastoma multiforme Prior low grade glioma that has progressed to high grade glioma following radiotherapy and/or chemotherapy allowed Measurable disease by MRI or CT scan PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin normal SGOT or SGPT no greater than 2.5 times upper limit of normal Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance greater than 60 mL/min Cardiovascular: No myocardial infarction, stroke, or congestive heart failure within the past 3 months Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 1 month after study No serious active infection or medical illness that would preclude compliance HIV negative No history of gastrointestinal disorders that would interfere with absorption of study drug No other malignancy within the past 5 years except curatively treated carcinoma in situ of the cervix or breast, or basal cell or squamous cell skin cancer No hypersensitivity to tetracyclines or its derivatives PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent filgrastim (G-CSF) Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks since prior nitrosoureas) and recovered No more than 2 prior chemotherapy regimens Endocrine therapy: Not specified Radiotherapy: No prior large field radiotherapy (greater than 20% of total bone marrow) At least 3 months since other prior radiotherapy and recovered Surgery: No prior major upper gastrointestinal surgery At least 14 days since other prior major surgery Other: No other concurrent investigational agents No prolonged sun exposure

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: incyclinide|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent adult brain tumor, adult glioblastoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult giant cell glioblastoma, adult gliosarcoma