Treatment of High-grade Gliomas Using Hypofractionated Radiation Therapy -a Phase I Clinical Trial

Xue Xiaoying

Status: Completed

Conditions: Glioma; Radiotherapy, Intensity-Modulated; Maximum Tolerated Dose

Treatments: Radiation: hypofractionated radiation; Drug: Temozolomide chemotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT03082846

phase I clinical trial-gliomas

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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16 participants in 1 patient group

hypofractionated group

Experimental group

Description:

hypofractionated group using hypofractionated radiation with temozolomide chemotherapy: Malignant gliomas patients received concurrent postoperative radiotherapy and chemotherapy.Intensity-modulated radiotherapy is adopted, 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 in PTV1. The planning target volume (PTV2) remain unchanged with 2.5 Gy each time and a total of 50 Gy/20 f. Temozolomide is administered orally every day at 75 mg/m2 during radiotherapy and at 150-200 mg/m2 for 12 cycles following completion of chemoradiotherapy.

Treatment:

Radiation: hypofractionated radiation

Drug: Temozolomide chemotherapy