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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Radiation: Intensity-modulated radiation therapy; Drug: Paclitaxel liposome; Drug: Cisplatin; Drug: 5-Fluorouracil

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 215
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Hai Qiang Mai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Reduced dose group; After 2 cycles of induction chemotherapy with Paclitaxel Liposome, Cisplatin and 5-Fluorouracil, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (30 fractions). Patients also receive cisplatin once per three week for 3 cycles.	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.; Drug: 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.; Drug: 5-Fluorouracil; Patients receive 5-Fluorouracil by 3750mg/m2 civ120h with a total of three cycles.
EXPERIMENTAL: Standard dose group; After 2 cycles of induction chemotherapy with Paclitaxel Liposome,Cisplatin and 5-Fluorouracil, patients undergo standard-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cisplatin once per three week for 3 cycles.	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.; Drug: 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.; Drug: 5-Fluorouracil; Patients receive 5-Fluorouracil by 3750mg/m2 civ120h with a total of three cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Overall response rate	Tumour response rate was classified according to RECIST, version 1.1	2 years
Incidence of acute toxicity	Numbers of patients of treatment-related adverse events as assessed by CTCAE v4.0.	2 years
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Study Chair: Hai Qiang Mai, MD.PHD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 19, 2018
• Primary Completion (ANTICIPATED): December 31, 2021
• Study Completion (ANTICIPATED): December 30, 2023

Study Registration Dates

• First Submitted: June 8, 2018
• First Submitted That Met QC Criteria: September 11, 2018
• First Posted (ACTUAL): September 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 24, 2021
• Last Update Submitted That Met QC Criteria: August 23, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: IMRT; nasopharyngeal carcinoma; induction chemotherapy; Radiation dose
• Additional Relevant MeSH Terms: 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; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Cisplatin; Fluorouracil
• Other Study ID Numbers: B2018-020-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No