A Trial of One-week on/One-week Off Temozolomide Versus Continuous Dose-Intense Temozolomide in Patients With Glioblastoma Multiforme at First Relapse

The purpose of this study is to evaluate the clinical benefit and safety of two different Dose-Intense temozolomide regimens（one-week on/one-week off regimen versus continuous dose-intense regimen）in patients with glioblastoma at first relapse.

Study Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Temozolomide

• Study Type: Interventional
• Enrollment (Actual): 204
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants must have histopathologically-confirmed, supratentorial, glioblastoma.
2. Participants must have received first-line treatment regimen consisting of RT plus concomitant temozolomide followed by adjuvant temozolomide.
3. Participants must be first recurrence or progression of glioblastoma after first-line treatment regimen.
4. Participants must have demonstration of recurrent disease on MRI following prior therapy.
5. Participants must have bi-dimensionally measurable disease with a minimum measurement of 1 cm in one dimension on MRI performed within 14 days prior to first treatment. If receiving corticosteroids, participants must be on a stable or decreasing dose of corticosteroids for at least 5 days prior to baseline MRI.
6. Participants must have developed progressive disease after receiving prior therapy and must have an interval of at least 12 weeks from the completion of radiation and concomitant temozolomide therapy to study entry (unless progressive tumor growth is outside the radiation field or there is histopathological confirmation of recurrent tumor)
7. Age 18-75 years old.
8. Life expectancy of at least 12 weeks.
9. Karnofsky performance status at least 60
10. Participants must be able to adhere to the dosing and visit schedules, and agree to record medication times, concomitant medications, and adverse events (AEs) accurately and consistently in a daily diary.
11. 20 paraffinsections of glioblastoma tissue must be available.
12. Participants must have normal organ and marrow function as defined below: leukocytes >4.0×10^9/L，platelets >100×10^9/L，Hemoglobin > 10 g/dl，Serum creatinine< 1.5-fold upper normal range，AST and ALT <2-fold upper normal range, Alkaline phosphatase < 3-fold upper normal range.
13. Female and male subjects of childbearing potential must agree to use a medically accepted method of adequate contraception.

Exclusion Criteria:

1. Treatment with any chemotherapy other than temozolomide prior to enrollment.
2. Progressive or recurrent glioblastoma documented by MRI earlier than 12 weeks after completion of radiotherapy.
3. History of any other cancer.
4. HIV infection.
5. Women who are pregnant or breast feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm1 ,one-week on/one-week off regimen; One-week on/one-week off regimen is administered for 12 cycles of 28 days. Arm 1 receives temozolomide 150 mg/m2 daily during days 1 to 7 and 15 to 21 of each cycle.Treatment will continue until tumor progression, development of excessive toxicity, withdrawal of consent, or completion of 12 cycles.	Drug: Temozolomide; Other Names: Temodal
Experimental: Arm 2,continuous dose-intense regimen; Continuous dose-intense regimen is administered for 12 cycles of 28 days .Arm 2 receives temozolomide 50mg/m2 daily during days 1 to 28 of each cycle. Treatment will continue until tumor progression, development of excessive toxicity, withdrawal of consent, or completion of 12 cycles.	Drug: Temozolomide; Other Names: Temodal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progress-Free Survival at 6 months (PFS6)	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival(OS)	2 years
Progression free survival	2 years
Objective Response Rate	up to 52 weeks
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	up to 52 weeks

Collaborators and Investigators

• Sponsor: Beijing Sanbo Brain Hospital
• Investigators: Principal Investigator: Junping Zhang, MD, Beijing Sanbo Brain Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): March 1, 2020
• Study Completion (Actual): September 1, 2020

Study Registration Dates

• First Submitted: December 30, 2014
• First Submitted That Met QC Criteria: January 1, 2015
• First Posted (Estimated): January 5, 2015

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: relapse; Temozolomide; glioblastoma; glioblastoma at first relapse
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: 2014062501

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No