Efficacy Study of Radiotherapy Alone Versus CCRT With Temozolomide in Grade III Gliomas Without 1p/19q Codeletion

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2012 by Asan Medical Center
Sponsor:
Information provided by (Responsible Party):
Jong Hoon Kim, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01534845
First received: February 6, 2012
Last updated: February 16, 2012
Last verified: February 2012
  Purpose
  1. The management of anaplastic gliomas of WHO grade 3 is currently largely based on surgery followed by radiotherapy, of which prognosis remains still dismal with the median survival of 2-5 years. To date, the benefit of chemo for WHO grade 3 gliomas is unclear of modest at best with conventional cytotoxic agents, and the role of temozolomide for these entities still is not elucidated.
  2. Codeletion of chromosome 1p/19q is considered the most important marker of prognostic significance in WHO grade 3 gliomas.
  3. To project a randomized phase 2 screening trial examining the efficacy of concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide for WHO grade 3 gliomas without codeletion of chromosome 1p/19q.
  4. The prognostic significance of methylation status of MGMT and IDH1 mutation as molecular markers will be also assessed in each arm as key secondary analysis.

Condition Intervention Phase
Anaplastic Glioma of Brain
Loss of Chromosomes 1p/19q
Drug: Temozolomide (Temodal)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase 2 Study to Evaluate the Efficacy Between Only Radiotherapy Versus CCRT With Temozolomide in Newly Diagnosed Grade III Gliomas Without 1p/19q Codeletion

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • 2-year progression free survival(PFS) [ Time Frame: Assessed and followed for the duration of hospital stay, an expected average of 3 months ] [ Designated as safety issue: No ]
    Final primary end-point: 2 year PFS. Progression free survival(PFS) is defined as the time from randomization to progressive disease or death, which ever occurs earlier.


Secondary Outcome Measures:
  • 5-year overall survival (OS) [ Time Frame: assessed at 10 wks, 22 wks, 34 wks, and followed up every 4 months until documentation of death. ] [ Designated as safety issue: No ]
    final secondary end-point : 5-year OS. Overall survival is defined as the time from randomization to death, which ever occurs earlier.

  • 5-year progression-free survival (PFS) [ Time Frame: assessed at 10 wks, 22 wks, 34 wks, and followed up every 4 months until documentation of disease progression or death. ] [ Designated as safety issue: No ]
    final end-point : 5-year PFS

  • Safety (adverse events) [ Time Frame: up to 5 years ] [ Designated as safety issue: Yes ]
  • Methylation status of MGMT [ Time Frame: baseline ] [ Designated as safety issue: No ]
    confirmed by MS-PCR.

  • IDH mutation [ Time Frame: baseline ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: March 2012
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: only Radiotherapy
fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy
Active Comparator: CCRT with Temozolomide
RT with daily temozolomide (75 mg/m2/day, 7 days/week) from the first to the last day of radiotherapy) and adjuvant TMZ chemotherapy (150-200 mg/m2 po qd for 5 days q 28 days for 6 cycles).
Drug: Temozolomide (Temodal)
RT with daily temozolomide (75 mg/m2/day, 7 days/week) from the first to the last day of radiotherapy) and adjuvant TMZ chemotherapy (150-200 mg/m2 po qd for 5 days q 28 days for 6 cycles)
Other Name: Temodal

Detailed Description:

The role of chemotherapy for gliomas has been recently reappraised by the advent of temozolomide, especially for glioblastomas, and further investigation is now being directed to unveiling its optimal indications, dosing protocols, and the most relevant prognostic factors. Meanwhile, the management of anaplastic gliomas of WHO grade 3 (anaplastic astrocytomas, anaplastic oligodendrogliomas, and anaplastic oligoastrocytomas) is currently largely based on surgery followed by radiotherapy, of which prognosis remains still dismal with the median survival of 2-5 years. To date, the benefit of chemo for WHO grade 3 gliomas is unclear of modest at best with conventional cytotoxic agents, and the role of temozolomide for these entities still is not elucidated. Moreover, WHO grade 3 gliomas are now known to consist of heterogeneous groups of different histologic features, biological behaviors, and prognoses. Accordingly, relevant molecular markers are appreciated with the growing body of data that showing their implications on response to therapy and survival, including codeletion of chromosome 1p/19q, methylation status of methylguanine methyl transferase (MGMT), and isocitrate dehydrogenase (IDH) mutation.1,4-6,11 Among those, codeletion of chromosome 1p/19q is considered the most important marker of prognostic significance in WHO grade 3 gliomas.

One recent Korean prospective cohort study showed the potential survival benefit and safety of concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide for WHO grade 3 gliomas. In this study, however, the role of molecular markers such as codeletion of chromosome 1p/19q and MGMT methylation could not be determined because of small number of patients available. These results prompted this Korean group to project a randomized phase 2 screening trial examining the efficacy of concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide for WHO grade 3 gliomas without codeletion of chromosome 1p/19q. The basic concept of the present clinical trial is "a subgroup with expected worse prognosis according to the status of chromosome 1p/19q, i.e. one without codeletion of chromosome 1p/19q is to be managed more aggressively", to investigate the role of temozolomide. An aggressive therapy (surgery + concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide) will be compared to the conventional arm (surgery + radiotherapy only) in terms of its efficacy and safety for WHO grade 3 gliomas without chromosome 1p/19q codeletion. The prognostic significance of methylation status of MGMT and IDH1 mutation as molecular markers will be also assessed in each arm as key secondary analysis. Until now, there have been no such trials examining the efficacy and safety of temozolomide for WHO grade 3 gliomas based on prospective molecular stratification.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Newly diagnosed histologically proven supratentorial anaplastic gliomas.The histological diagnosis must be obtained from a neurosurgical resection or biopsy of a tumor including an open biopsy or stereotactic biopsy.
  • Absence of chromosome 1p/19q co-deletion
  • Age 18 years
  • Eastern Cooperative Oncology Group performance status of 0-1
  • Stable or decreasing dose of steroids for 5 days prior to randomization
  • Meets 1 of the following RPA classifications:class III-V
  • Adequate hematologic, renal, and hepatic function
  • Written informed consent

Exclusion criteria:

  • Prior chemotherapy within last 5 years
  • Prior radiotherapy of the head and neck area
  • Receiving concurrent investigational agents or has received an investigational agent within 30 days prior to randomization
  • Planned surgery for other diseases (e.g. dental extraction)
  • History of malignancy. Subjects with curatively treated cervical carcinoma in situ or basal cell carcinoma of the skin, or subjects who have been free of other malignancies for 5 years are eligible for this study
  • Pregnant or lactating women
  • Subject who disagree to follow acceptable methods of contraception
  • Concurrent illness including unstable heart disease despite appropriate treatment, history of myocardial infarction within 6 months, serious neurological or psychological disease, and uncontrolled infection
  • Subject unable to undergo Gd-MRI
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01534845

Contacts
Contact: Jeong Hoon Kim, MD, PhD. +82230103559 ext +8223010355 jhkim1@amc.seoul.kr

Locations
Korea, Republic of
Asan Medical Center Not yet recruiting
Seoul, Korea, Republic of, 138-736
Contact: jeong hoon kim, PhD.MD    82-2-3010-3559 ext direct    jhkim1@amc.seoul.kr   
Principal Investigator: jeong hoon kim, PhD.MD         
Sponsors and Collaborators
Jong Hoon Kim
Investigators
Principal Investigator: Jeong Hoon Kim, Professor Asan Medical Center
Study Director: Jae Young Kim, professor SNUH
  More Information

No publications provided

Responsible Party: Jong Hoon Kim, Professor, Department of Neurological Surgery, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01534845     History of Changes
Other Study ID Numbers: KNOG-1101
Study First Received: February 6, 2012
Last Updated: February 16, 2012
Health Authority: Korea: Food and Drug Administration

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 14, 2014