Temozolomide in Treating Patients With Recurrent High-Grade Glioma

Recurrent Central Nervous System Neoplasm Clinical Trial

Official title:

Phase II Study of 7 Days On/7 Days Off Temozolomide in Patients With High-Grade Glioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00619112
• Other study ID #: UCSF-07107
• Secondary ID: SPRI-UCSF-H44867
• Status: Completed
• Phase: Phase 2
• First received: February 19, 2008
• Last updated: January 5, 2018
• Start date: October 2007
• Est. completion date: September 2012

Study information

• Verified date: January 2018
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 recurrent high-grade glioma.

Description:

OBJECTIVES:

Primary

• Determine the efficacy, as measured by 6-month progression-free survival, of a dose-intense temozolomide treatment schedule in patients with recurrent high-grade glioma.

Secondary

• Assess the toxicities of this dose-intense temozolomide.

• Determine the overall survival of patients treated with this dose-intense schedule.

• Determine whether methylation status of the MGMT gene within patients' tumors predicts greater efficacy (progression-free survival), in patients treated on this protocol.

• Determine whether patients' tumors have functional alterations of the mismatch repair (MMR) system by PCR analysis for microsatellite instability (MSI) and whether such alterations may influence outcome in patients treated on this protocol.

• Determine how initial success with temozolomide may influence outcome in recurrent patients treated on this protocol by evaluating patients progressing after two first-line adjuvant courses of temozolomide, patients progressing within 6 months after the 6th adjuvant course of temozolomide, and patients progressing 6 months after temozolomide is voluntarily discontinued.

OUTLINE: Patients receive oral temozolomide once daily on days 1-7 and days 15-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Formalin-fixed paraffin-embedded tissue blocks or unstained paraffin slides from available surgical samples are evaluated for molecular abnormalities in the tumor, including (but not limited to) MGMT status and microsatellite instability.

After completion of study therapy, patients are followed every 3 months for survival.

PROJECTED ACCRUAL: A total of 40 patients with WHO II grade 4 tumors (glioblastoma multiforme [GBM]) and 20 patients with WHO II grade 3 tumors (non-GBM) will be accrued for this study.

Other known NCT identifiers

• NCT00539552

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: September 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Patients with radiographically proven recurrent, intracranial malignant glioma will be eligible for this protocol.

• All patients must sign an informed consent

• Patients must have had external beam radiation; there is no limit to the number of prior chemotherapies used.

• Patients must be > 18 years old, and with a life expectancy > 8 weeks.

• Patients must have a Karnofsky performance status of > 60.

• At the time of registration: Patients must have recovered from the toxic effects of prior therapy:

• Patients must have adequate bone marrow function.

• Patients must have shown unequivocal radiographic evidence for tumor progression by MRI

• Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply: They have recovered from the effects of surgery. Residual disease following resection of recurrent intracranial malignant glioma is not mandated for eligibility into the study.

• Patients must have failed prior radiation therapy and must have an interval of greater than or equal to 42 days from the completion of radiation therapy to study entry.

• Patients with prior therapy that included interstitial brachytherapy, stereotactic radiosurgery, or Gliadel wafers must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or MR spectroscopy or surgical documentation of disease.

• Male and female patients with reproductive potential must use an approved contraceptive method

Exclusion Criteria

• Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy

• Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.

• Patients must not have active infection or serious intercurrent medical illness.

• Patients must not be pregnant/breast feeding and must agree to practice adequate contraception.

Related Conditions & MeSH terms

• Central Nervous System Neoplasms
• Glioma
• Nervous System Neoplasms
• Recurrent Central Nervous System Neoplasm

Intervention

Drug:
• temozolomide
single arm study

Locations

Country	Name	City	State
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	6 Month Progression-free Survival	Efficacy of dose-intense temozolomide treatment schedule, as measured by 6 months progression-free survival	First day of treatment until progression or until 6 months mark
Secondary	Progression-free Survival (PFS) Based on Tumor MGMT (O(6)-Methylguanine-DNA Methyltransferase) Promoter Methylation Status.	Progression-free survival data (obtained for Primary Outcome Measure) was correlated with tumor MGMT (O(6)-methylguanine-DNA methyltransferase) promoter methylation status, obtained from patients as part of the study.	First day of treatment until progression or until 6 months mark
Secondary	Overall Survival		up to 2 years after treatment
Secondary	Patients With Tumors With Functional Alterations of the Mismatch Repair (MMR) System	PCR analysis of tumor tissue for microsatellite instability (MSI). Tissue was obtained during surgeries prior this study.	prior to start of study
Secondary	Patients Progressing After Two First-line Adjuvant Courses of Temozolomide		After two first-line adjuvant courses of temozolomide
Secondary	Patients Progressing Within 6 Months After 6th Adjuvant Course of Temozolomide		Within 6 months after 6th adjuvant course of temozolomide
Secondary	Patients Progressing 6 Months After Temozolomide is Voluntarily Discontinued		From beginning of voluntarily temozolomide discontinued up to 6 months