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

Glioma 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03082846
• Other study ID #: phase I clinical trial-gliomas
• Status: Completed
• Phase: N/A
• First received: February 22, 2017
• Last updated: March 17, 2017
• Start date: January 1, 2014
• Est. completion date: December 3, 2016

Study information

• Verified date: March 2017
• Source: The Second Hospital of Hebei Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: December 3, 2016
• Est. primary completion date: November 7, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Glioma
• Maximum Tolerated Dose
• Radiotherapy, Intensity-Modulated

Intervention

Radiation:
• hypofractionated radiation
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 in PTV1, until dose-limiting toxicity is present,the highest target single dose is 4 Gy/f. The planning target volume (PTV2) including the 2 cm region around surgical cavity and residual tumor remain unchanged, with 2.5 Gy each time and a total of 50 Gy/20f.

Drug:
• Temozolomide chemotherapy
Temozolomide(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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Xue Xiaoying

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the maximum tolerated dose(MTD)	Safety and tolerability of hypofractionated simultaneous integrated boost intensity modulated radiation therapy (SIB-IMRT) combined with standard temozolomide chemotherapy.; The maximum tolerated dose of hypofractionated radiation combined with concurrent temozolomide in newly diagnosed highgrade glioma is being explored.	1year
Secondary	Progression free survival	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year.	1 year