Hypofractionated Versus Conventionally Fractionated Radiotherapy for Initial Distant Metastases Nasopharyngeal Carcinoma

A Multicenter, Prospective, Randomized, Phase II Trial Evaluating Hypofractionated Versus Conventionally Fractionated Radiotherapy for Initial Distant Metastases Nasopharyngeal Carcinoma

Radiotherapy is an important treatment for initial distant metastases nasopharyngeal carcinoma. Total dose and fraction size are important prognostic factors for survival, although to our knowledge the optimal model has not been well determined to date. The purpose of this clinical trial is to investigate the optimal radiation dose to investigate the feasibility of decreasing the total dose and increasing the fraction size with the objective of achieving a better balance between local control and severe late complications. for initial distant metastases nasopharyngeal carcinoma with definitive radiotherapy.

Study Overview

• Status: Completed
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Radiation: Hypofraction radiation; Radiation: Standard dose IMRT

Detailed Description

PRIMARY OBJECTIVES:

I. To determine if hypofractionated with a smaller total dose radiation is not inferior to standard-dose radiation in progression-free survival for initial distant metastases nasopharyngeal carcinoma .

SECONDARY OBJECTIVES:

I. To evaluate if hypofractionated with a low total dose radiation is not inferior to standard-dose radiation in overall survival and locoregional failure-free survival for initial distant metastases nasopharyngeal carcinoma II. To evaluate if hypofractionated with a low total dose radiation with chemotherapy decrease treatment-related toxicities

OUTLINE:

Patients are randomized to one of the two treatment arms

ARM 1: Patients receive hypofractionated with a low total dose radiation with induced chemotherapy and adjuvant chemotherapy.Hypofractionated dose IMRT: GTVnx 60Gy, GTVnd 60Gy, PTV1 50Gy and PTV2 45Gy in 25 fractions, 5 days/week.

Induced chemotherapy: Paclitaxel 135mg/m2 D1+Cisplatin 75mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles. After radiation, patients receive adjuvant chemotherapy Paclitaxel 135mg/m2 D1+Cisplatin 75mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles.

ARM 2: Patients receive standard-dose radiation with concurrent chemotherapy. Standard-dose IMRT: GTVnx 69.69Gy, GTVnd 60-68Gy, PTV1 59.4Gy and PTV2 54Gy in 33 fractions, 5 days/week.

Induced chemotherapy: Paclitaxel 135mg/m2 D1+Cisplatin 75mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles. After radiation, patients receive adjuvant chemotherapy Paclitaxel 135mg/m2 D1+Cisplatin 75mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles.

After completion of study therapy, patients are followed up every 3-4 months for 2 years, then every 6 months for 3 years.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guilin, China
    • Guangxi Naxishan Hospital
  • Linshan, China
    • Linshan people's hospital
  • Wuzhou, China
    • Wuzhou Red Cross Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type) Tumor staged as any T or any N with M (according to the 8th AJCC edition).
2. No pregnant female
3. Age between 18-70
4. Normal complete blood count level (hemoglobin >10 g/dL, white blood cells ≥4000/μL, platelets ≥100 000/μL)
5. Normal hepatic functions (serum total bilirubin ≤1.6 mg/dL, serum transminase < 2.5 times higher than upper limit)
6. Normal renal function (serum creatinine ≤1.5 mg/dL, creatinine clearance ≥60 mL/min)
7. Karnofsky performance status (KPS) score of at least 70
8. Without radiotherapy or chemotherapy
9. Patients must give signed informed consent

Exclusion Criteria:

1. Other or mixed pathological type
2. age > 70 years or <18 years
3. Prior chemotherapy, radiation, surgical resection or target therapy of the primary tumor;
4. Significant medical or psychiatric illnesses that in the physician's judgment (uncontrolled coronary heart disease, cardiomyopathy and/or heart failure requiring hospitalization. Uncontrolled hypertension or history of myocardial infarction within one year. Uncontrolled diabetes mellitus. Acute bacterial or fungal infection requiring intravenous antibiotics;
5. Refused to sign informed consent form
6. Concurrent pregnancy or lactation
7. History of a second malignancy other than nasopharyngeal carcinoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypofractionated dose IMRT; Patients receive hypofractionated with a low total dose radiation with induced chemotherapy and adjuvant chemotherapy.	Radiation: Hypofraction radiation; Hypofractionated dose IMRT: GTVnx 60Gy, GTVnd 60Gy, PTV1 50Gy and PTV2 45Gy in 25 fractions, 5 days/week. Induced chemotherapy: Paclitaxel 135mg/m2 D1+Cisplatin 80mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles. After radiation, patients receive adjuvant chemotherapy Paclitaxel 135mg/m2 D1+Cisplatin 80mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles.
Experimental: Standard-dose IMRT; Patients receive standard-dose radiation therapy with induced chemotherapy and adjuvant chemotherapy..	Radiation: Standard dose IMRT; Standard dose IMRT: GTVnx 69.69Gy, GTVnd 60-68Gy, PTV1 54.9Gy and PTV2 54Gy in 33 fractions, 5 days/week. Induced chemotherapy: Paclitaxel 135mg/m2 D1+Cisplatin 80mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles. After radiation, patients receive adjuvant chemotherapy Paclitaxel 135mg/m2 D1+Cisplatin 80mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	The time from the first day of therapy to locoregional relapse, distant relapse or tumor-related death	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The time from the first day of therapy to death or last follow-up.	2 years
Locoregional relapse-free survival	The time from the first day of treatment to the time of first locoregional relapse	2 years
Distant metastasis-free survival	The time from the first day of treatment to the time of first distant metastasis	2 years

Collaborators and Investigators

• Sponsor: Wei Jiang
• Collaborators: Wuzhou Red Cross Hospital; Lingshan people's Hospital; Guangxi Naxishan Hospital; Nanning Monority Hospital
• Investigators: Study Director: Wei Jiang, Ph.D., Guilin Medical University, China

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2018
• Primary Completion (Actual): June 10, 2020
• Study Completion (Actual): April 10, 2022

Study Registration Dates

• First Submitted: July 14, 2018
• First Submitted That Met QC Criteria: July 14, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): August 3, 2023
• Last Update Submitted That Met QC Criteria: August 2, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: nasopharyngeal carcinoma; Hypofractionated Radiation; initial distant metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplastic Processes; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Neoplasm Metastasis
• Other Study ID Numbers: GLMU-03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No