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

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

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.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Drug: incyclinide

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.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham Comprehensive Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital - Atlanta
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney kimmel comprehensive cancer center at johns hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157-1082
      • Comprehensive Cancer Center at Wake Forest University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-4283
      • University of Pennsylvania Cancer Center
  • Texas
    • San Antonio, Texas, United States, 78284-7811
      • University of Texas Health Science Center at San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: New Approaches to Brain Tumor Therapy Consortium
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Pamela Z. New, MD, The University of Texas Health Science Center at San Antonio

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2000
• Study Completion (Actual): November 1, 2006

Study Registration Dates

• First Submitted: December 10, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): June 21, 2013
• Last Update Submitted That Met QC Criteria: June 20, 2013
• Last Verified: May 1, 2003

More Information

Terms related to this study

• Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; recurrent adult brain tumor; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neoplasms by Site; Nervous System Neoplasms; Central Nervous System Neoplasms
• Other Study ID Numbers: CDR0000067379; NABTT-9809; JHOC-NABTT-9809