Anaplastic Glioma of BrainPhase 2NCT01534845
Efficacy Study of Radiotherapy Alone Versus CCRT With Temozolomide in Grade III Gliomas Without 1p/19q Codeletion
A Phase 2 study testing Temozolomide (Temodal) in people with Anaplastic Glioma of Brain and Loss of Chromosomes 1p/19q, run by Jong Hoon Kim at 1 site in South Korea.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Anaplastic Glioma of Brain, Loss of Chromosomes 1p/19q
- What is being tested?
- Temozolomide (Temodal)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteSouth Korea
- Study dates
- Mar 2012to Feb 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
- 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.
- Codeletion of chromosome 1p/19q is considered the most important marker of prognostic significance in WHO grade 3 gliomas.
- 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 prognostic significance of methylation status of MGMT and IDH1 mutation as molecular markers will be also assessed in each arm as key secondary analysis.
Read the 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.
- Being tested
- Temozolomide (Temodal)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Temozolomide (Temodal)Drug
Also called 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)
| Study group | Role | What they receive |
|---|---|---|
| only Radiotherapy | No intervention | fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy |
| CCRT with Temozolomide | Active comparator | 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). Receives: Drug: Temozolomide (Temodal) |
What is being measured
The primary outcome is the main question the study is designed to answer.
2-year progression free survival(PFS)
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.
Measured: Assessed and followed for the duration of hospital stay, an expected average of 3 months
Secondary outcomes (5)
5-year overall survival (OS)
final secondary end-point : 5-year OS. Overall survival is defined as the time from randomization to death, which ever occurs earlier.
Measured: assessed at 10 wks, 22 wks, 34 wks, and followed up every 4 months until documentation of death.
5-year progression-free survival (PFS)
final end-point : 5-year PFS
Measured: assessed at 10 wks, 22 wks, 34 wks, and followed up every 4 months until documentation of disease progression or death.
Safety (adverse events)
Measured: up to 5 years
Methylation status of MGMT
confirmed by MS-PCR.
Measured: baseline
IDH mutation
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2012 (estimated)
- Study startMar 2012
- Primary completionFeb 2015
- Study completionFeb 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anaplastic Glioma of BrainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jong Hoon Kim
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jong Hoon Kim, Asan Medical Center
- Investigators
- Jeong Hoon Kim, Professor, Principal investigator, Asan Medical CenterJae Young Kim, professor, Study director, SNUH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01534845
- Sponsor's protocol ID
- KNOG-1101
- Status last verified
- Jul 2015
- First submitted
- 6 Feb 2012
- Last updated
- 9 Jul 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01534845
- Acronym / sponsor ID
- KNOG-1101
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Jong Hoon KimUniversity, hospital or other
- Study start
- Mar 2012
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2017 (estimated)
- First posted
- 17 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- 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.
- Codeletion of chromosome 1p/19q is considered the most important marker of prognostic significance in WHO grade 3 gliomas.
- 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 prognostic significance of methylation status of MGMT and IDH1 mutation as molecular markers will be also assessed in each arm as key secondary analysis.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| only Radiotherapy | No intervention | –fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy |
| CCRT with Temozolomide | Active comparator | 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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Temozolomide (Temodal)Also: TemodalRT 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 | CCRT with Temozolomide |
Primary outcome
2-year progression free survival(PFS)
Time frame: Assessed and followed for the duration of hospital stay, an expected average of 3 months
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.
5 secondary outcomes
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.
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.
Safety (adverse events)
Time frame: up to 5 years
Methylation status of MGMT
Time frame: baseline
IDH mutation
Time frame: baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeong Hoon Kim, Professor principal investigator
Asan Medical Center
Jae Young Kim, professor study director
SNUH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Temozolomide (Temodal) in people with Anaplastic Glioma of Brain and Loss of Chromosomes 1p/19q, run by Jong Hoon Kim at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
2-year progression free survival(PFS) (time frame: Assessed and followed for the duration of hospital stay, an expected average of 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2015.