Reduced-dose Radiotherapy for Low-risk Stage III Patients With Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

A Phase II Trial of Induction Chemotherapy Followed by Cisplatin With Low Dose vs. Standard Dose IMRT in Stage III Nasopharyngeal Carcinoma Patients With Pretreatment EBV DNA<4000 Copy/ml

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03668730
• Other study ID #: B2018-020-01
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 19, 2018
• Est. completion date: December 30, 2023

Study information

• Verified date: August 2021
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To study the 2-year PFS (progression-free survival) of patients with stage III nasopharyngeal carcinoma of pretreatment EBV DNA<4000 copy/ml treated with induction chemotherapy followed by two different doses of intensity-modulated radiation therapy and cisplatin.

Description:

To explore the 2 year PFS of patients with stage III nasopharyngeal carcinoma of pretreatment EBV DNA<4000 copy/ml treated with induction chemotherapy followed by reduced-dose radiation and cisplatin. The enrolled patients will receive 2 cycles of TPF regimen induction chemotherapy, if radiographic CR/PR and EBV DNA=0 after induction chemotherapy, the patients will be delivered by 60 Gy IMRT combined with 3 cycles of cisplatin concurrent chemotherapy. If radiographic SD/PD or EBV DNA>0 after induction chemotherapy, the patients will receive a total of 70 Gy IMRT combined with 3 cycles of cisplatin concurrent chemotherapy.

The included patients will be treated with 2 cycles of TPF regimen induction chemotherapy and 60Gy IMRT combined with cisplatin concurrent chemotherapy. The TPF regimen is consist of paclitaxel liposome 135mg/m2 d1, cisplatin 25mg/m2d1-d3 and 5-Fu 3750mg/m2 civ120h, with a total of two cycles. Concurrent cisplatin chemotherapy is delivered with dose of 100mg/m2, a total of three cycles. The third cycle of cisplatin concurrent chemotherapy is allowed to be delivered within one week after IMRT finished.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 215
• Est. completion date: December 30, 2023
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Pathological diagnosis of NPC(WHO II or III).

2. Stage III(8thAJCC/UICC staging system) and pretreatment EBVDNA<4000opies/ml.

3. Aged 18-70 years?

4. ECOG = 0-1?

5. HGB=90 g/L,WBC=4×109 /L,PLT=100×109 /L.

6. ALT,AST<2.5 fold of ULN;TBIL<2.0×ULN?

7. CCR=60ml/min or Cr<1.5×ULN?

8. Signed informed consent

Exclusion Criteria:

1. WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma.

2. Age <18 or >70years.

3. Treatment with palliative intent.

4. Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer.

5. Pregnancy or lactation.

6. History of previous radiotherapy (except for non-melanomatous skin cancers outside intended RT treatment volume).

7. Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes.

8. Any severe intercurrent disease, which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control (fasting plasma glucose >1.5×ULN), and emotional disturbance.

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma

Intervention

Radiation:
• Intensity-modulated radiation therapy
Patients undergo low-dose OR standard dose IMRT based on their radiographic response to induction chemotherapy

Drug:
• Paclitaxel liposome
Patients receive Paclitaxel liposome by 135mg/m2 with a total of two cycles.
• Cisplatin
Patients receive Cisplatin by 25mg/m2 on day1-day3 with a total of two cycles as induction chemotherapy ; patients receive cisplatin by 100mg/m2 with a total of three cycles as concurrent chemotherapy.
• 5-Fluorouracil
Patients receive 5-Fluorouracil by 3750mg/m2 civ120h with a total of three cycles.

Locations

Country	Name	City	State
China	Hai Qiang Mai	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS(progression free survival)	Defined from date of registration to date of first documentation of progression and/or distant metastasis,or death due to any cause. The primary study population for this endpoint is patients who were confirmed post-induction CR /PR and EBV DNA=0 and subsequently received 60Gy radiation therapy.	2 years
Secondary	Overall Survival(OS)	Defined from date of registration to date of first documentation of death from any cause or censored at the date of the last follow-up.	2 years
Secondary	Locoregional relapse-free survival(LRFS)	Defined from date of registration to date of first documentation of locoregional relapse or until the date of the last follow-up visit.	2 years
Secondary	Distant metastasis-free survival(DMFS)	Defined from date of registration to date of first documentation of distant metastases or until the date of the last follow-up visit.	2 years
Secondary	Overall response rate	Tumour response rate was classified according to RECIST, version 1.1	2 years
Secondary	Incidence of acute toxicity	Numbers of patients of treatment-related adverse events as assessed by CTCAE v4.0.	2 years
Secondary	Incidence of late toxicity	Numbers of patients of late radiation toxicities were assessed using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme.	2 years
Secondary	Change of ADC( apparent diffusion coefficient ) value of DWI(Diffusion-Weighted MRI) of patients predictive of failure	The ADC value of each patient of Diffusion-Weighted MRI at pretreatment and after induction chemotherapy was calculated were evaluated independently on a work station.	2 years
Secondary	Change of QoL	QoL scores were assessed for each scale by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30) before induction chemotherapy, before radiotherapy, at the end of radiotherapy, at 3 months after radiotherapy, at 6 months after radiotherapy and 12 months after radiotherapy.	1 years
Secondary	Change of EORTC quality of life questionnaire(QLQ) Head and Neck score	QoL scores were assessed by using EORTC quality of life questionnaire(QLQ) Head and Neck. The QLQ-H&N35 is composed of seven multi-item symptom scales (pain, swallowing, sensation, speech, eating from a social,perspective, social interactions, and sexuality) and 11 single-item symptom scales (teeth, opening mouth,dry mouth, sticky saliva, coughing, felt ill, pain medication use, nutritional supplementation, feeding tube requirement, weight loss, and weight gain). All of the scales and items ranged in score from 0 to 100. A high score for a functional or global QoL scale represents a relatively high/healthy level of functional or global QoL, whereas a high score for a symptom scale or item represents a high number of symptoms or problems.	1 years
Secondary	Plasma EBV DNA copy number	Plasma EBV DNA copy number with either reduced or standard dose radiotherapy was assessed by qRT-PCR at pretreatment. The predictive value of plasma EBV DNA copy number was assessed by survival analysis.	2 years