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

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004147
• Other study ID #: CDR0000067379
• Secondary ID: NABTT-9809JHOC-N
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: December 10, 1999
• Last updated: June 20, 2013
• Start date: July 2000
• Est. completion date: November 2006

Study information

• Verified date: May 2003
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: November 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• incyclinide

Locations

Country	Name	City	State
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Henry Ford Hospital	Detroit	Michigan
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	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
New Approaches to Brain Tumor Therapy Consortium	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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- — View Citation