Clinical trial NCT00004147: COL-3 in Treating Patients With Progressive or Recurrent Brain Tumors
Official title: A Phase I/II Study of Col-3 Administered on a Continuous Daily Oral Schedule in Patients With Recurrent High-Grade Astrocytoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: recurrent adult brain tumor
adult glioblastoma
adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult giant cell glioblastoma
adult gliosarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital - Atlanta
state: Georgia
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center at San Antonio
name: Pamela Z. New, MD
role: STUDY_CHAIR
References:
citation: 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.