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Temozolomide in Treating Patients With Recurrent High-Grade Glioma

Primary Purpose

Recurrent Central Nervous System Neoplasm

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

temozolomide

About this trial

This is an interventional treatment trial for Recurrent Central Nervous System Neoplasm focused on measuring adult glioblastoma, adult gliosarcoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma, recurrent adult brain tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

UCSF Helen Diller Family Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Temozolomide

Arm Description

single arm trial; Patients treated with temozolomide at a dose of 150mg/m2 daily for seven consecutive days of every other week. One 28-day cycle will include treatment with temozolomide on days 1-7 and days 15-21 with no treatment on days 8-14

Outcomes

Primary Outcome Measures

6 Month Progression-free Survival

Efficacy of dose-intense temozolomide treatment schedule, as measured by 6 months progression-free survival

Secondary Outcome Measures

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.

Overall Survival

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.

Patients Progressing After Two First-line Adjuvant Courses of Temozolomide

Patients Progressing Within 6 Months After 6th Adjuvant Course of Temozolomide

Patients Progressing 6 Months After Temozolomide is Voluntarily Discontinued

Full Information

NCT ID

NCT00619112

First Posted

February 19, 2008

Last Updated

January 5, 2018

Sponsor

University of California, San Francisco

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00619112

Brief Title

Temozolomide in Treating Patients With Recurrent High-Grade Glioma

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2018

Overall Recruitment Status

Completed

Study Start Date

October 2007 (undefined)

Primary Completion Date

December 2011 (Actual)

Study Completion Date

September 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of California, San Francisco

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Recurrent Central Nervous System Neoplasm

Keywords

adult glioblastoma, adult gliosarcoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma, recurrent adult brain tumor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Temozolomide

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

temozolomide

Other Intervention Name(s)

temodar

Intervention Description

single arm study

Primary Outcome Measure Information:

Title

6 Month Progression-free Survival

Description

Efficacy of dose-intense temozolomide treatment schedule, as measured by 6 months progression-free survival

Time Frame

First day of treatment until progression or until 6 months mark

Secondary Outcome Measure Information:

Title

Progression-free Survival (PFS) Based on Tumor MGMT (O(6)-Methylguanine-DNA Methyltransferase) Promoter Methylation Status.

Description

Time Frame

First day of treatment until progression or until 6 months mark

Title

Overall Survival

Time Frame

up to 2 years after treatment

Title

Patients With Tumors With Functional Alterations of the Mismatch Repair (MMR) System

Description

PCR analysis of tumor tissue for microsatellite instability (MSI). Tissue was obtained during surgeries prior this study.

Time Frame

prior to start of study

Title

Patients Progressing After Two First-line Adjuvant Courses of Temozolomide

Time Frame

After two first-line adjuvant courses of temozolomide

Title

Patients Progressing Within 6 Months After 6th Adjuvant Course of Temozolomide

Time Frame

Within 6 months after 6th adjuvant course of temozolomide

Title

Patients Progressing 6 Months After Temozolomide is Voluntarily Discontinued

Time Frame

From beginning of voluntarily temozolomide discontinued up to 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nicholas A. Butowski, MD

Organizational Affiliation

University of California, San Francisco

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Susan M. Chang, MD

Organizational Affiliation

University of California, San Francisco

Official's Role

Principal Investigator

Facility Information:

Facility Name

UCSF Helen Diller Family Comprehensive Cancer Center

City

San Francisco

State/Province

California

ZIP/Postal Code

94115

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

24670608

Citation

Han SJ, Rolston JD, Molinaro AM, Clarke JL, Prados MD, Chang SM, Berger MS, DeSilva A, Butowski NA. Phase II trial of 7 days on/7 days off temozolmide for recurrent high-grade glioma. Neuro Oncol. 2014 Sep;16(9):1255-62. doi: 10.1093/neuonc/nou044. Epub 2014 Mar 26.

Results Reference

derived

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Temozolomide in Treating Patients With Recurrent High-Grade Glioma

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