CCRT With Temozolomide Versus RT Alone in Patients With IDH Wild-type/TERT Promoter Mutation Grade II/III Gliomas

January 18, 2017 updated by: Tao Jiang, Beijing Tiantan Hospital

A Prospective Study of Concurrent Chemoradiotherapy With Temozolomide Versus Radiation Therapy Alone in Patients With IDH Wild-type/TERT Promoter Mutation Grade II/III Gliomas

The management of lower-grade gliomas (Diffuse low-grade and intermediate-grade gliomas, WHO II and III) is largely based on surgery followed by radiotherapy. Recent studies showed that lower-grade glioma patients with IDH wild-type (IDH-wt) and TERT promoter mutation (TERTp-mut) had dismal clinical outcomes. These results suggested that current treatment strategies are not adequate for this subtype of lower-grade glioma.

The present study aims to examine the efficacy and safety of concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide for lower- grade glioma patients with IDH-wt and TERTp-mut.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) are infiltrative neoplasms that arise most often in the cerebral hemispheres of adults and include astrocytomas, oligodendrogliomas, and oligoastrocytomas. The management of lower-grade gliomas is largely based on surgery followed by radiotherapy.

Lower-grade gliomas have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Consequently, clinicians increasingly rely on genetic classification to guide clinical decision making. Mutations in IDH1 and IDH2 characterize the majority of lower-grade gliomas in adults and define a subtype that is associated with a favorable prognosis. Mutations of the telomerase reverse transcriptase (TERT) promoter, which result in enhanced telomerase activity and lengthened telomeres, have been observed in several human cancers including glioma. Accumulating evidence suggest that TERT promoter mutation is another molecular marker which can stratify lower-grade gliomas into prognostic subgroups in combination with IDH mutation. In our previous study, patients(28/377, 7.4%) who had lower-grade gliomas with IDH wild-type (IDH-wt) and TERT promoter mutation (TERTp-mut) had the poorest clinical outcomes (median OS, 27.7mo; 5-year OS, 29%). These results were accordant with the recent studies and suggested that current treatment strategies are not adequate for this subtype of lower-grade glioma.

Radiotherapy plus temozolomide has emerged as a new standard of care for patients with good PS non-elderly glioblastoma. There are some data that support temozolomide as adjuvant therapy for lower-grade glioma. Given that the IDH-wt/TERTp-mut subgroup of lower-grade gliomas has dismal prognosis, a more aggressive therapy such as concurrent chemoradiotherapy seems to be reasonable. The present study aims to examine the efficacy and safety of concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide for lower-grade glioma patients with IDH-wt and TERTp-mut. Half the patients will be randomly assigned to receive concurrent chemoradiotherapy (surgery + concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide) and half the patients will be randomly assigned to receive conventional therapy (surgery + radiotherapy only).

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Xiao-Guang Qiu, M.D.
  • Phone Number: 0086-010-67096611
  • Email: ttyy6611@126.com

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100050
        • Recruiting
        • Beijing Tiantan Hospital
        • Contact:
        • Principal Investigator:
          • Tao Jiang, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed supratentorial Diffuse low-grade and intermediate-grade gliomas (World Health Organization grades II and III )
  • IDH wild-type and TERT promoter mutation
  • Age > 18
  • Karnofsky performance score > 60
  • Neutrophilic granulocyte count > 1500/µl
  • Platelet count > 100 000/µl
  • Hemoglobin > 10 g/dl
  • Serum creatinine < 1.5 times the lab's upper normal limit
  • AST or ALT < 1.5 times the lab's upper normal limit
  • Adequate medical health to participate in this study
  • No previous systemic chemotherapy
  • No previous radiotherapy to the brain
  • Written informed consent

Exclusion Criteria:

  • Serious medical or neurological condition with a poor prognosis
  • Contraindications to radiotherapy or temozolomide chemotherapy
  • Patient unable to follow procedures, visits, examinations described in the study
  • Second cancer requiring radiotherapy or chemotherapy
  • Inability to undergo gadolinium-contrasted MRIs
  • Pregnant women or nursing mothers can not participate in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Chemoradiotherapy with Temozolomide
Patients undergo intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy 5 days a week for 6 weeks (for a total of 60 Gy) and receive temozolomide PO QD (75 mg/m2/day, 7 days/week) for up to 7 weeks. Beginning 4 weeks after completion of chemotherapy and radiation therapy, patients receive temozolomide PO QD on days 1-5 (150-200 mg/m2). Treatment with temozolomide repeats every 28 days for up to 12 courses
Radiation: Radiotherapy
Drug: Temozolomide
RT with daily temozolomide (75 mg/m2/day, 7 days/week for up to 7 weeks) and adjuvant temozolomide (150-200 mg/m2 PO QD for 5 days, repeats every 28 days for up to 12 courses).
Active Comparator: Radiotherapy alone
Patients undergo intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy 5 days a week for 6 weeks (for a total of 60 Gy)
Radiation: Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: Up to 2 years
Overall survival is defined as the time from randomization to death.
Up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival(PFS)
Time Frame: Up to 2 years
Progression free survival(PFS) is defined as the time from randomization to progressive disease or death. A combination of neurological examination and MRI brain scan used to define progression.
Up to 2 years
The incidence and severity of adverse events associated with treatment with RT alone and combined with temozolomide chemotherapy; according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0.
Time Frame: Up to 2 years
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Tiantan Hospital

Collaborators

Beijing Shijitan Hospital, Capital Medical University
Beijing Neurosurgical Institute

Investigators

  • Principal Investigator: Tao Jiang, M.D., Beijing Tiantan Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 26, 2016

Primary Completion (Anticipated)

December 1, 2017

Study Completion (Anticipated)

December 1, 2018

Study Registration Dates

First Submitted

May 4, 2016

First Submitted That Met QC Criteria

May 6, 2016

First Posted (Estimate)

May 9, 2016

Study Record Updates

Last Update Posted (Estimate)

January 20, 2017

Last Update Submitted That Met QC Criteria

January 18, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CFMD 2016-2-1073

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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