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Concurrent Chemotherapy for the Intermediate Risk Nasopharyngeal Carcinoma In Intensity-modulated Radiotherapy Era

Primary Purpose

Nasopharyngeal Carcinoma

Status

Unknown status

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

IMRT

Cisplatin

About this trial

This is an interventional treatment trial for Nasopharyngeal Carcinoma focused on measuring Nasopharyngeal carcinoma, Concurrent chemoradiotherapy, intermediate risk, intensity-modulated radiotherapy

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type.
Tumor staged as T1-2N1/T2-3N0(according to the 7th AJCC edition).
No evidence of distant metastasis (M0).
Satisfactory performance status: Karnofsky scale (KPS) ≥ 70.
Adequate marrow: leucocyte count ≥ 4000/μL, hemoglobin ≥ 120g/L for male, ≥ 120g/L for female , and platelet count ≥ 100000/μL.
Normal liver function test: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) < 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) ≤ 2.5×ULN, and bilirubin ≤ ULN.
Adequate renal function: creatinine clearance ≥ 60 ml/min.
Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion Criteria:

Neck lymph node with extracapsular spread. Maximal axial diameter of neck lymph node ≥30mm, positive neck lymph node at level IV and/or Vb.
Pretreatment plasma EBV DNA level ≥4000 copy/ml.
WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma.
Age > 65 or < 18.
Treatment with palliative intent.
Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer.
Pregnancy or lactation (consider pregnancy test in women of child-bearing age and emphasize effective contraception during the treatment period).
History of previous RT (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

Sun Yat-sen University Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

RT group

CCRT group

Arm Description

intensity modulated-radiotherapy (IMRT) alone: Patients receive intensity modulated-radiotherapy (IMRT) alone

IMRT and concurrent cisplatin Patients receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles

Outcomes

Primary Outcome Measures

Failure-free survival

The failure-free survival rate will be estimated using the Kaplan-Meier method for each arm from the date of randomization to the date of treatment failure or death from any cause, whichever is first. Their differences will be compared between treatment arms using the log-rank test.

Secondary Outcome Measures

Overall survival

The overall survival rate will be estimated using the Kaplan-Meier method for each arm from randomization to death from any cause. Their differences will be compared between treatment arms using the log-rank test.

Locoregional failure-free survival

The locoregional failure-free survival will be estimated using the Kaplan-Meier method for each arm from randomization to the first locoregional failure. Their differences will be compared between treatment arms using the log-rank test.

Distant failure-free survival

The distant failure-free survival will be estimated using the Kaplan-Meier method for each arm from randomization to the first remote failure. Their differences will be compared between treatment arms using the log-rank test.

Rates of participants with adverse events

Acute and late toxicities will be documented according to the Common Terminology Criteria for Adverse Events version 3.0 and/or the Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group. Rates of the toxicities will be estimated using a binomial distribution along and will be compared using Fisher's exact test between the 2 treatment arms.

Full Information

NCT ID

NCT02633202

First Posted

December 3, 2015

Last Updated

December 11, 2018

Sponsor

Sun Yat-sen University

Collaborators

Fifth Affiliated Hospital, Sun Yat-Sen University, First People's Hospital of Foshan, Guilin Medical University, China

1. Study Identification

Unique Protocol Identification Number

NCT02633202

Brief Title

Concurrent Chemotherapy for the Intermediate Risk Nasopharyngeal Carcinoma In Intensity-modulated Radiotherapy Era

Official Title

Prospective Non-inferior Clinical Trial Comparing Concurrent Chemoradiotherapy or Radiotherapy Alone in Patients With Intermediate Risk Nasopharyngeal Carcinoma in Intensity-modulated Radiotherapy Era

Study Type

Interventional

2. Study Status

Record Verification Date

December 2018

Overall Recruitment Status

Unknown status

Study Start Date

November 2015 (undefined)

Primary Completion Date

December 2019 (Anticipated)

Study Completion Date

December 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sun Yat-sen University

Collaborators

Fifth Affiliated Hospital, Sun Yat-Sen University, First People's Hospital of Foshan, Guilin Medical University, China

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Currently, concurrent chemoradiotherapy with/without sequential chemotherapy is the standard treatment modality for intermediate risk NPC (stage II and T3N0M0) according to the National Comprehensive Cancer Network guideline. However these recommendations were based on the evidence in the two-dimensional conventional radiotherapy (2DCRT) era. The introduction of intensity-modulated radiotherapy (IMRT) in NPC treatment has brought substantial better treatment outcomes than 2DCRT. It has been questioned whether additional concurrent chemotherapy is still necessary for intermediate risk NPC within the excellent framework of IMRT. Thus, the investigators jointly conduct the first non-inferior randomized trial to determine the value of concurrent chemotherapy with cisplatin for intermediate risk NPC patients treated with IMRT. Given the results of clinical studies mentioned above,the investigators decide to adopt the concurrent regimen to be cisplatin 100 mg/m2 on day 1, 22, 43

Detailed Description

Currently, concurrent chemoradiotherapy with/without sequential chemotherapy is the standard treatment modality for intermediate risk NPC (stage II and T3N0M0) according to the National Comprehensive Cancer Network guideline. However these recommendations were based on the evidence in the two-dimensional conventional radiotherapy (2DCRT) era. The introduction of intensity-modulated radiotherapy (IMRT) in NPC treatment has brought substantial better treatment outcomes than 2DCRT. It has been questioned whether additional concurrent chemotherapy is still necessary for intermediate risk NPC within the excellent framework of IMRT. Thus, the investigators jointly conduct the first non-inferior randomized trial to determine the value of concurrent chemotherapy with cisplatin for intermediate risk NPC patients treated with IMRT. Given the results of clinical studies mentioned above, the investigators decide to adopt the concurrent regimen to be cisplatin 100 mg/m2 on day 1, 22, 43

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nasopharyngeal Carcinoma

Keywords

Nasopharyngeal carcinoma, Concurrent chemoradiotherapy, intermediate risk, intensity-modulated radiotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

338 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

RT group

Arm Type

Experimental

Arm Description

intensity modulated-radiotherapy (IMRT) alone: Patients receive intensity modulated-radiotherapy (IMRT) alone

Arm Title

CCRT group

Arm Type

Active Comparator

Arm Description

IMRT and concurrent cisplatin Patients receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles

Intervention Type

Radiation

Intervention Name(s)

IMRT

Other Intervention Name(s)

Intensity-modulated radiation therapy

Intervention Description

Intensity modulated-radiotherapy (IMRT) is given as 2.0-2.30 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumor

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Other Intervention Name(s)

Concurrent cisplatin regimen

Intervention Description

concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles during IMRT

Primary Outcome Measure Information:

Title

Failure-free survival

Description

Time Frame

3 Year

Secondary Outcome Measure Information:

Title

Overall survival

Description

Time Frame

3 Year

Title

Locoregional failure-free survival

Description

Time Frame

3 Year

Title

Distant failure-free survival

Description

Time Frame

3 Year

Title

Rates of participants with adverse events

Description

Time Frame

3 Year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type. Tumor staged as T1-2N1/T2-3N0(according to the 7th AJCC edition). No evidence of distant metastasis (M0). Satisfactory performance status: Karnofsky scale (KPS) ≥ 70. Adequate marrow: leucocyte count ≥ 4000/μL, hemoglobin ≥ 120g/L for male, ≥ 120g/L for female , and platelet count ≥ 100000/μL. Normal liver function test: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) < 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) ≤ 2.5×ULN, and bilirubin ≤ ULN. Adequate renal function: creatinine clearance ≥ 60 ml/min. Patients must be informed of the investigational nature of this study and give written informed consent. Exclusion Criteria: Neck lymph node with extracapsular spread. Maximal axial diameter of neck lymph node ≥30mm, positive neck lymph node at level IV and/or Vb. Pretreatment plasma EBV DNA level ≥4000 copy/ml. WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma. Age > 65 or < 18. Treatment with palliative intent. Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer. Pregnancy or lactation (consider pregnancy test in women of child-bearing age and emphasize effective contraception during the treatment period). History of previous RT (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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Lei Chen, M.D.

Phone

+86-20-87343096

chenlei@sysucc.org.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lei Chen, M.D.

Organizational Affiliation

Sun Yat-sen University

Official's Role

Study Chair

Facility Information:

Facility Name

Sun Yat-sen University Cancer Center

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lei Chen, M.D.

Phone

+86-20-87343096

chenlei@sysucc.org.cn

12. IPD Sharing Statement

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Citation

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Concurrent Chemotherapy for the Intermediate Risk Nasopharyngeal Carcinoma In Intensity-modulated Radiotherapy Era

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