Back to resultsReduced-dose Radiotherapy for Low-risk Stage III Patients With Nasopharyngeal Carcinoma
Primary Purpose
Nasopharyngeal Carcinoma
Status
Active
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Intensity-modulated radiation therapy
Paclitaxel liposome
Cisplatin
5-Fluorouracil
Sponsored by
About this trial
This is an interventional treatment trial for Nasopharyngeal Carcinoma focused on measuring nasopharyngeal carcinoma, IMRT, Radiation dose, induction chemotherapy
Eligibility Criteria
Inclusion Criteria:
- Pathological diagnosis of NPC(WHO II or III).
- Stage III（8thAJCC/UICC staging system) and pretreatment EBVDNA<4000opies/ml.
- Aged 18-70 years。
- ECOG = 0-1。
- HGB≥90 g/L，WBC≥4×109 /L，PLT≥100×109 /L.
- ALT,AST<2.5 fold of ULN；TBIL<2.0×ULN。
- CCR≥60ml/min or Cr<1.5×ULN。
- Signed informed consent
Exclusion Criteria:
- WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma.
- Age <18 or >70years.
- Treatment with palliative intent.
- Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer.
- Pregnancy or lactation.
- History of previous radiotherapy (except for non-melanomatous skin cancers outside intended RT treatment volume).
- Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes.
- 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.
Sites / Locations
- Hai Qiang Mai
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Reduced dose group
Standard dose group
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
Overall response rate
Tumour response rate was classified according to RECIST, version 1.1
Incidence of acute toxicity
Numbers of patients of treatment-related adverse events as assessed by CTCAE v4.0.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03668730
Brief Title
Reduced-dose Radiotherapy for Low-risk Stage III Patients With Nasopharyngeal Carcinoma
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 19, 2018 (Actual)
Primary Completion Date
December 31, 2021 (Anticipated)
Study Completion Date
December 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nasopharyngeal Carcinoma
Keywords
nasopharyngeal carcinoma, IMRT, Radiation dose, induction chemotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
215 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Reduced dose group
Arm Type
Experimental
Arm Description
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.
Arm Title
Standard dose group
Arm Type
Experimental
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
Intensity-modulated radiation therapy
Intervention Description
Patients undergo low-dose OR standard dose IMRT based on their radiographic response to induction chemotherapy
Intervention Type
Drug
Intervention Name(s)
Paclitaxel liposome
Intervention Description
Patients receive Paclitaxel liposome by 135mg/m2 with a total of two cycles.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
5-Fluorouracil
Intervention Description
Patients receive 5-Fluorouracil by 3750mg/m2 civ120h with a total of three cycles.
Primary Outcome Measure Information:
Title
PFS(progression free survival)
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Overall Survival(OS)
Description
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.
Time Frame
2 years
Title
Locoregional relapse-free survival(LRFS)
Description
Defined from date of registration to date of first documentation of locoregional relapse or until the date of the last follow-up visit.
Time Frame
2 years
Title
Distant metastasis-free survival(DMFS)
Description
Defined from date of registration to date of first documentation of distant metastases or until the date of the last follow-up visit.
Time Frame
2 years
Title
Overall response rate
Description
Tumour response rate was classified according to RECIST, version 1.1
Time Frame
2 years
Title
Incidence of acute toxicity
Description
Numbers of patients of treatment-related adverse events as assessed by CTCAE v4.0.
Time Frame
2 years
Title
Incidence of late toxicity
Description
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.
Time Frame
2 years
Title
Change of ADC( apparent diffusion coefficient ) value of DWI(Diffusion-Weighted MRI) of patients predictive of failure
Description
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.
Time Frame
2 years
Title
Change of QoL
Description
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.
Time Frame
1 years
Title
Change of EORTC quality of life questionnaire(QLQ) Head and Neck score
Description
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.
Time Frame
1 years
Title
Plasma EBV DNA copy number
Description
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.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pathological diagnosis of NPC(WHO II or III).
Stage III（8thAJCC/UICC staging system) and pretreatment EBVDNA<4000opies/ml.
Aged 18-70 years。
ECOG = 0-1。
HGB≥90 g/L，WBC≥4×109 /L，PLT≥100×109 /L.
ALT,AST<2.5 fold of ULN；TBIL<2.0×ULN。
CCR≥60ml/min or Cr<1.5×ULN。
Signed informed consent
Exclusion Criteria:
WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma.
Age <18 or >70years.
Treatment with palliative intent.
Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer.
Pregnancy or lactation.
History of previous radiotherapy (except for non-melanomatous skin cancers outside intended RT treatment volume).
Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hai Qiang Mai, MD.PHD
Organizational Affiliation
Sun Yat-sen University
Official's Role
Study Chair
Facility Information:
Facility Name
Hai Qiang Mai
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Reduced-dose Radiotherapy for Low-risk Stage III Patients With Nasopharyngeal Carcinoma
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