Clinical trial NCT03082846: Treatment of High-grade Gliomas Using Hypofractionated Radiation Therapy -a Phase I Clinical Trial
Official title: Treatment of High-grade Gliomas Using Escalating Doses of Hypofractionated Simultaneous Integrated Boost-intensity Modulated Radiation Therapy in Combination With Temozolomide - a Modified Phase I Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glioma
Radiotherapy, Intensity-Modulated
Maximum Tolerated Dose
Keywords: malignant glioma
intensity modulated radiation therapy
simultaneous integrated boost
hypofractionation
temozolomide
maximum tolerated dose
Lead sponsor: The Second Hospital of Hebei Medical University
Sponsor class: OTHER
First posted: 2017-03-17
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Postoperative conventional radiation at 60 Gy/30f is currently still considered the standard radiotherapy mode for high-grade gliomas; however, the efficacy is still unsatisfactory. Studies in recent years have shown that hypofractionated simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) has certain survival benefits over other fractionation methods; but, the best hypofractionation mode and its efficacy have not been confirmed. The purpose of this study is to investigate the maximum tolerated dose (MTD) of hypofractionated SIB-IMRT with stepwise escalating of doses combined with temozolomide (TMZ) for the treatment of malignant gliomas.

Detailed description: Background: Postoperative conventional radiation at 60 Gy/30f is currently still considered the standard radiotherapy mode for high-grade gliomas; however, the efficacy is still unsatisfactory. Studies in recent years have shown that hypofractionated simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) has certain survival benefits over other fractionation methods; but, the best hypofractionation mode and its efficacy have not been confirmed. The purpose of this study is to investigate the maximum tolerated dose (MTD) of hypofractionated SIB-IMRT with stepwise escalating of doses combined with temozolomide (TMZ) for the treatment of malignant gliomas. Methods: Malignant gliomas patients receive concurrent postoperative radiotherapy and chemotherapy. The simultaneous integrated boost-intensity modulated technology is adopted to increase both the dose in the surgical cavity and residual tumor (PTV1). The dose at each fraction is gradually increased from 2.8 Gy/f (total of 20 times) with an escalating dose interval of 0.4 Gy. The planning target volume (PTV2) including the 2cm region around surgical cavity and residual tumor remain unchanged, with 2.5 Gy each time and a total of 50 Gy/20f. The subsequent group of patients is advanced to the next dose level until dose-limiting toxicity (DLT) is present. The dose, one level lower than the DLT, is the MTD. The highest target single dose is 4 Gy/f. TMZ is administered orally every day at 75 mg/m2 during radiotherapy and at 150-200 mg/m2 for 12 cycles following completion of chemoradiotherapy.

Eligibility criteria: Inclusion Criteria:

1. Postoperative grades III and IV glioma patients confirmed by pathology.
2. The ages are between 18-70 years.
3. Karnofsky performance score（KSP）≧60.
4. Expected survival period ≧3 months.
5. Blood routine and liver and kidney functions are normal.
6. Receive cranial MRI examination after 48 h of surgery.
7. Radiotherapy is performed after 2-4 weeks of surgery.
8. Patients with restricted lesions and non-diffuse growth.
9. Maximum diameter of the residual tumor, surgical cavity, and primary tumor bed are ≦6 cm.

Exclusion Criteria:

1. Lesions are in the brain stem and thalamus.
2. Pregnant and lactating women.
3. Secondary primary malignant tumor.
4. Severe pulmonary infection.
5. Combination with mental illness or another disease that require hospitalization.
6. Patients had received chemotherapy or brain radiotherapy previously.

Primary outcomes:
measure: the maximum tolerated dose(MTD)
timeFrame: 1year
Secondary outcomes:
measure: Progression free survival
timeFrame: 1 year
Other outcomes:
Locations:
Study officials:
affiliation: Department of Radiotherapy
name: xiaoying xue, doctor
role: STUDY_DIRECTOR
References: