Combination Chemotherapy for Patients With Brain Cancer

A Phase II Trial of Paclitaxel and Topotecan With Filgrastim in Patients With Recurrent or Refractory Glioblastoma Multiforme or Anaplastic Astrocytoma

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: Phase II trial to study the effectiveness of combination chemotherapy using paclitaxel and topotecan, plus G-CSF, in treating patients with glioblastoma multiforme or anaplastic astrocytoma that is refractory or recurrent.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Drug: paclitaxel; Biological: filgrastim; Drug: topotecan hydrochloride

Detailed Description

OBJECTIVES: I. Determine the response rate in patients with refractory or recurrent glioblastoma multiforme or anaplastic astrocytoma treated with paclitaxel (TAX) and topotecan (TOPO) with granulocyte colony-stimulating factor (G-CSF) support. II. Determine survival in these patients. III. Describe the toxicity of TAX/TOPO/G-CSF. IV. Evaluate tumor p53 expression in relation to response to TAX/TOPO/G-CSF.

OUTLINE: All patients receive paclitaxel, topotecan, and G-CSF every 3 weeks for at least 2 courses and until 2 courses beyond maximum response. Patients are followed every 3 months for 2 years, then every 6 months for relapse and survival.

PROJECTED ACCRUAL: A total of 35 patients will be entered if there are 1-3 responses in the first 20 patients.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center

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: Biopsy proven glioblastoma multiforme or anaplastic astrocytoma Central pathologic review at Dartmouth-Hitchcock Medical Center, including assay for tumor p53 expression No anaplastic oligodendroglioma No mixed oligodendroastrocytoma Recurrent or progressive disease following radiotherapy documented by CT or MRI within 2 weeks of entry

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60%-100% Hematopoietic: WBC at least 3,000 ANC at least 1,500 Platelets at least 100,000 Hepatic: Bilirubin no greater than 1.0 mg/dL AST/ALT no greater than 2.5 times normal Renal: Creatinine no greater than 1.5 mg/dL Other: No documented sensitivity to E. coli-derived products No major medical or psychiatric illness that would interfere with therapy or compliance with scheduled follow-up No pregnant or nursing women Adequate contraception required of fertile patients

PRIOR CONCURRENT THERAPY: No prior taxanes or topoisomerase I inhibitors At least 4 weeks since chemotherapy (6 weeks since nitrosoureas) At least 4 weeks since radiotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Investigators: Study Chair: Camilo E Fadul, MD, Dartmouth-Hitchcock Medical Center

Study record dates

Study Major Dates

• Study Start: August 1, 1996
• Primary Completion (Actual): April 1, 2001
• Study Completion (Actual): December 1, 2001

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: April 5, 2004
• First Posted (Estimate): April 6, 2004

Study Record Updates

• Last Update Posted (Estimate): October 27, 2011
• Last Update Submitted That Met QC Criteria: October 26, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; recurrent adult brain tumor; adult anaplastic astrocytoma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neoplasms by Site; Nervous System Neoplasms; Central Nervous System Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Paclitaxel; Topotecan
• Other Study ID Numbers: D9607; NCI-V96-0955 (Other Grant/Funding Number: NCI)