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

NCT ID: NCT00004147

Last Updated: 2013-06-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-07-31
• Study Completion Date: 2006-11-30

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Primary Study Purpose: TREATMENT

Interventions

incyclinide

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

New Approaches to Brain Tumor Therapy Consortium

OTHER

Sponsor Role: lead

Principal Investigators

Pamela Z. New, MD

Role: STUDY_CHAIR

The University of Texas Health Science Center at San Antonio

Locations

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Emory University Hospital - Atlanta

Atlanta, Georgia, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, United States

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Countries

United States

References

Rudek MA, New P, Mikkelsen T, Phuphanich S, Alavi JB, Nabors LB, Piantadosi S, Fisher JD, Grossman SA. Phase I and pharmacokinetic study of COL-3 in patients with recurrent high-grade gliomas. J Neurooncol. 2011 Nov;105(2):375-81. doi: 10.1007/s11060-011-0602-9. Epub 2011 May 6.

Reference Type: RESULT

PMID: 21547395 (View on PubMed)

Other Identifiers

NABTT-9809

Identifier Type: -

Identifier Source: secondary_id

JHOC-NABTT-9809

Identifier Type: -

Identifier Source: secondary_id

CDR0000067379

Identifier Type: -

Identifier Source: org_study_id