Temozolomide in Treating Patients With Low-Grade Glioma

A Phase II Study of Temozolomide (TEMODAR) in the Treatment of Adult Patients With Supratentorial Low Grade Glioma

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well temozolomide works in treating patients with supratentorial low-grade glioma.

Study Overview

• Status: Completed
• Conditions: CNS Tumor, Adult
• Intervention / Treatment: Drug: temozolomide

Detailed Description

OBJECTIVES:

Primary

• Determine the efficacy of temozolomide, defined as response rate (complete and partial response), in patients with supratentorial mixed low-grade glioma.

Secondary

• Assess the safety profile of temozolomide in patients with supratentorial low-grade glioma.
• Assess the time to tumor progression in patients treated with temozolomide.

OUTLINE: Patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Family Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically proven supratentorial low-grade (grade II) glioma of any of the following histologic subtypes:

  • Oligodendroglioma
  • Astrocytoma
  • Oligoastrocytoma

• Has undergone surgical resection or biopsy within 35 days after diagnosis of low-grade glioma

  • Study treatment must begin between 14 days and 4 months after surgical resection or biopsy
• Evaluable disease by gadolinium-MRI

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• Creatinine < 1.5 times upper limit of normal (ULN)
• BUN < 1.5 times ULN
• Bilirubin < 1.5 times ULN
• SGOT < 2.5 times ULN
• Alkaline phosphatase < 2 times ULN
• Life expectancy > 12 weeks
• No nonmalignant systemic disease resulting in the patient being a poor medical risk
• No acute infection requiring intravenous antibiotics
• No frequent vomiting or medical condition that would interfere with oral medication intake (e.g., partial bowel obstruction)

• No other concurrent malignancies except surgically cured carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin

  • Prior malignancies must be in remission for ≥ 5 years
• No known HIV positivity
• No AIDS-related illness
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior radiotherapy, interstitial brachytherapy, or radiosurgery for low-grade glioma
• No prior biological therapy or chemotherapy for low-grade glioma
• No other concurrent chemotherapy
• No concurrent radiotherapy or biological therapy
• No concurrent prophylactic growth factors
• No concurrent epoetin alfa
• No other concurrent investigational drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Temozolomide	Drug: temozolomide; Chemotherapy; Other Names: Temodar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate (Complete and Partial Response)	Assessment of treatment response was determined by MRI in conjunction with neurological examination and steroid requirement assessment derived from Macdonald's criteria. Complete response was defined as complete disappearance of lesion on consecutive MRI scans with stable or improved neuro exam and steroids. Partial response was defined as a 50% reduction in lesion size or that tumor burden was "definitely better" than prior scan with stable or improved neuro exam and steroids.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Tumor Progression	Progressive disease was defined as definite enlargement of any existing lesion or any new lesion based on modified Macdonald's criteria.	time from registration until date of the first documented progression, an average of 1 year
Safety Profile	Number of participants with treatment related grade 2-4 adverse events as defined by CTCAE 3.0	Time from registration up to 13 months

Collaborators and Investigators

• Sponsor: University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: May 1, 1999
• Primary Completion (Actual): September 25, 2014
• Study Completion (Actual): June 12, 2017

Study Registration Dates

• First Submitted: April 11, 2006
• First Submitted That Met QC Criteria: April 11, 2006
• First Posted (Estimate): April 12, 2006

Study Record Updates

• Last Update Posted (Actual): February 7, 2019
• Last Update Submitted That Met QC Criteria: January 22, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: adult diffuse astrocytoma; adult oligodendroglioma; adult mixed glioma; adult pilocytic astrocytoma; adult pineal gland astrocytoma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Glioma; Central Nervous System Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: CDR0000448883; 99102 (Other Identifier: UCSF Cancer Center Protocol Number); BTRC-9902; H7858-16278-07 (Other Identifier: UCSF IRB)