To determine if dose-intensifying the adjuvant temozolomide component of the chemoradiation treatment enhances treatment efficacy as measured by overall survival.
ID
Source
Brief title
Condition
- Nervous system neoplasms malignant and unspecified NEC
- Nervous system neoplasms malignant and unspecified NEC
- Nervous system, skull and spine therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine if dose-intensifying the adjuvant temozolomide component of the
chemoradiation treatment enhances treatment efficacy as measured by overall
survival.
Secondary outcome
1. To validate the association between tumor MGMT gene promotr methylation
status and treatment response.
2. To determine if dose-intensifying the adjuvant temozolomide component of the
chemoradiation treatment enhances treatment efficacy as measured by
progression-free survival.
3. To determine in patients with unmethylated MGMT if dose-intensifying the
adjuvant temozolomide component of the chemoradiation treatment enhances
treatment efficacy (overall and progression-free survival) compared with
patients receiving conventional temozolomide dosing.
4.To determine in patients with methylated MGMT if dose-intensifying the
adjuvant temozolomide component of the chemoradiation treatment enhances
treatment efficacy overall and progression-free survival) compared with
patients receiving conventional temozolomide dosing.
5. To compare and record the toxicities of the conventional and dose-intense
chemotherapy regims.
6. To evaluate wether 6-month progression-free survival is associated with
overall survival.
Background summary
The prognosis of patients with glioblastoma multiforme is poor. Chemotherapy
with temozolomide improves, when administered concomitant and adjuvant, the
treatmentresult of radiotherapy. Dose-intensification of chemotherapy may
further improve the treatment outcome.
Study objective
To determine if dose-intensifying the adjuvant temozolomide component of the
chemoradiation treatment enhances treatment efficacy as measured by overall
survival.
Study design
Phase III randomised, open intervention study.
Intervention
In both treatmentarms patients will have radiation of the primary tumour area (
60 Gy in 2 Gy fractions) combined with daily temozolomide ( 75 mg/m2) , during
maximum 49 days, followed by adjuvant chemotherapy:
* Conventional arm: Temozolomide 150 - 200 mg/m2 for 5 consecutive days of a
28-day cyclus. Duration: 6 - 12 cycli
* Experimental arm: Temozolomide 75-100 mg/m2 for 21 consecutive days in a
28-day cyclus. Duration 6 - 12 cylci.
Study burden and risks
The extra burden constists of a maximum of 24 venous punctions in the period of
the adjuvant chemotherapy and pregnancy test before treatment. At the start of
this study dose-intensification, according to the information known at that the
moment, has demonstrated to be safe without extra complications.
After the review in June 2007 the studycoördinators had to conclude that the
risk known for temozolomide could be more likely to occur due to the dose-dense
schedule or worse if the event did occur.
Avenue Mounierlaan 83, Bte 11
B1200 Brussels
BE
Avenue Mounierlaan 83, Bte 11
B1200 Brussels
BE
Listed location countries
Age
Inclusion criteria
1. Histopathologically proven diagnosis of glioblastoma. Since gliosarcoma is a variant of glioblastoma, gliosarcoma is an eligible diagnosis.
2. Patients must have at least 1 block of tissues available for analysis of MGMT status.
3. Diagnosis must be made by open surgical biopsy or excision.
4. The tumor must have supratentorial component.
5. Patients must have recovered from the effects of surgery, post-operative infection, and other complications before study registration.
6. A diagnostic cotnrast-enhanced MRI ( or CT-scan if MRI is not available) of the brain preoperatively and postoperatively prior to the initiation of radiotherapy, within 28 days prior to study registration.
7. Therapy must begin within 5 weeks after surgery.
8. Karnofsky performance status more or equal then 60.
9. Age >= 18 years.
Exclusion criteria
1. Prior invasive malignacy unless disease free for more then 3 years.
2. Recurrent or multifocal malignant gliomas.
3. Histopathologically diagnosis made only by stereotactic biopsy.
4. Metastases detected below the tentorium or beyond the cranial vault.
5. Prior chemotherapy or radiosensitizers for cancers of the head and neck region.
65. Prior radiotherapy to the head or neck, resulting in overlap of radiation fields.
7. Severe, active co-morbidity:
* Unstrable angina and/or congestive heart failure requiring hospitalization.
* Transmural myocardial infarction within the last 6 months.
* COPD exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
* Hepatic insufficiency resulting in clinical jaundices and/or coagulation defects.
* Acquired Immune Deficiency Syndrome based upon current CDC definition; HIV testing is not required.
* Major illnesses or psychiatric impairments that in the investigator's opinion will prevent adminstiration or completion of protocol therapy.
* Active connectieve tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patients at high risk for radiaton toxicity.
8. Women of childbearing potrential and men who are secually active and not willing/able to use medically acceptabel forms of contraception.
9. Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study drug.
10. Prior allergic reaction to temozolomide.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2005-005177-29-NL |
| ClinicalTrials.gov | NCT00304031 |
| CCMO | NL13696.028.06 |