Clinical trial NCT00005855: Efaproxiral Plus Carmustine in Treating Patients With Progressive or Recurrent Malignant Glioma
Official title: A Phase I/II Study to Evaluate the Safety and Tolerance of Escalating Doses of RSR13 Administered With a Fixed Dose of BCNU Every Six Weeks in Patients With Recurrent Malignant Glioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: adult glioblastoma
adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
recurrent adult brain tumor
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
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of efaproxiral when given with carmustine and to see how well they work in treating patients with progressive or recurrent malignant glioma.

Detailed description: OBJECTIVES:

* Evaluate the safety and tolerability of escalating doses of efaproxiral (RSR13) when administered concurrently with carmustine in patients with progressive or recurrent malignant glioma.
* Determine the maximum tolerated dose (MTD) of RSR13 when administered with carmustine in this patient population.
* Determine the pharmacokinetic profile of this regimen in these patients.
* Estimate the efficacy of this regimen at the MTD in these patients.

OUTLINE: This is a nonrandomized, open-label, multicenter, dose-escalation study of efaproxiral (RSR13).

Patients receive RSR13 IV over 30 minutes followed 30 minutes later by carmustine IV over 1-2 hours on day 1. Treatment repeats every 6 weeks for a maximum of 6 courses in the absence of unacceptable toxicity or disease progression.

Cohorts of 6-12 patients receive escalating doses of RSR13 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 or 5 of 12 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with RSR13 and carmustine at the recommended phase II dose.

Patients are followed at 6 weeks and then every 2 months thereafter.

PROJECTED ACCRUAL: A maximum of 48 patients will be accrued for the phase I portion of this study. A maximum of 47 patients will be accrued for the phase II portion of this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed malignant glioma that is progressive or recurrent after radiotherapy with or without chemotherapy

  * Anaplastic astrocytoma
  * Anaplastic oligodendroglioma
  * Glioblastoma multiforme
* Prior low-grade glioma allowed provided progression has occurred after radiotherapy with or without chemotherapy and then high-grade glioma is found on biopsy
* Measurable disease by serial 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
* Hemoglobin at least 10 g/dL
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 2.0 mg/dL
* Alkaline phosphatase no greater than 3 times upper limit of normal (ULN)
* SGOT and SGPT no greater than 3 times ULN

Renal:

* Creatinine no greater than 2.0 mg/dL

Pulmonary:

* Resting oxygen saturation on room air at least 90% by pulse oximetry
* FVC, DLCO, and FEV_1 at least 50% of normal

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No other serious concurrent medical illness that would preclude study compliance
* No other prior malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 3 weeks since prior investigational biologics

Chemotherapy:

* See Disease Characteristics
* No prior nitrosoureas for glioma
* No more than 1 prior chemotherapy regimen
* At least 4 weeks since prior chemotherapy
* No prior efaproxiral

Endocrine therapy:

* Concurrent corticosteroids (e.g., dexamethasone) allowed

Radiotherapy:

* See Disease Characteristics
* At least 90 days since prior radiotherapy

Surgery:

* Not specified

Other:

* At least 3 weeks since other prior investigational drugs or devices

Primary outcomes:
measure: Safety and tolerability
measure: Maximum tolerated dose
measure: Pharmacokinetic profile
measure: Efficacy
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 at University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
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: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
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, Houston
name: Pamela Z. New, MD
role: STUDY_CHAIR
References: