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The Role of Induction Gemcitabine and Cisplatin in Locoregionally Advanced Nasopharyngeal Carcinoma in the Era of IMRT

Primary Purpose

Nasopharyngeal Carcinoma

Status

Active

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

Gemcitabine

cisplatin

Intensity-modulated Radiotherapy

About this trial

This is an interventional treatment trial for Nasopharyngeal Carcinoma focused on measuring nasopharyngeal carcinoma, induction chemotherapy

Eligibility Criteria

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

Inclusion Criteria:

Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma (including WHO II or III).
Tumor staged as T1-4N2-3或T3-4N0-1M0 (according to the 7th AJCC edition).
Satisfactory performance status: Karnofsky scale (KPS) ≥ 70.
Adequate marrow: leucocyte count ≥ 4000/μL, hemoglobin ≥ 90g/L and platelet count ≥ 100000/μL.
Adequate liver function: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) < 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) ≤ 2.5×ULN, and bilirubin ≤1.5×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:

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Experimental

Active Comparator

Arm Description

Induction chemotherapy+IMRT gemcitabine and cisplatin regimen Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 2 cycles before radiotherapy, and then receive intensity modulated-radiotherapy (IMRT).

IMRT and concurrent cisplatin Patients receive intensity modulated-radiotherapy (IMRT), concurrently with weekly cisplatin 40 mg/m² up to 7cycles.

Outcomes

Primary Outcome Measures

Failure-free survival

Failure-free survival rate is calculated from the date of randomization to the date of treatment failure or death from any cause, whichever is first.

Secondary Outcome Measures

Overall survival

Overall survival is calculated from randomization to death from any cause.

Locoregional failure-free survival

Locoregional failure-free survival is calculated from randomization to the first locoregional failure.

Distant failure-free survival

Distant failure-free survival is calculated from randomization to the first remote failure.

Overall response rate

Overall response rate at 3 months after completion of IMRT

Number of participants with adverse events

Incidence of acute and late toxicity

Quality of life during treatment

Quality of life is measured by FACIT questionnaire.

Full Information

NCT ID

NCT02460887

First Posted

May 28, 2015

Last Updated

October 25, 2022

Sponsor

Sun Yat-sen University

1. Study Identification

Unique Protocol Identification Number

NCT02460887

Brief Title

The Role of Induction Gemcitabine and Cisplatin in Locoregionally Advanced Nasopharyngeal Carcinoma in the Era of IMRT

Official Title

A Randomized Trial Comparing Induction Gemcitabine and Cisplatin Plus Intensity-modulated Radiotherapy With Concurrent Cisplatin Plus Intensity-modulated Radiotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 2015 (undefined)

Primary Completion Date

April 2022 (Actual)

Study Completion Date

April 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sun Yat-sen University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to verify that induction gemcitabine and cisplatin plus intensity-modulated radiotherapy (IMRT) is non-inferior to concurrent weekly cisplatin plus IMRT for patients with locoregionally advanced nasopharyngeal carcinoma (NPC).

Detailed Description

Patients with non-keratinizing NPC T1-4N2-3或T3-4N0-1M0 (UICC/AJCC 7th edition) are randomly assigned to receive induction chemotherapy or CCRT alone. Patients in experimental group receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 2 cycles before intensity-modulated radiotherapy (IMRT). Patients in control group receive IMRT concurrently with weekly cisplatin 40 mg/m² up to 7cycles. IMRT is given as 2.0-2.33 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. Our primary endpoint is failure-free survival (FFS). Secondary end points include overall survival (OS), locoregional failure-free survival (LR-FFS), distant failure-free survival (D-FFS) rates and toxic effects. All efficacy analyses are conducted in the intention-to-treat population, and the safety population include only patients who receive their randomly assigned treatment.

6. Conditions and Keywords

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

Nasopharyngeal Carcinoma

Keywords

nasopharyngeal carcinoma, induction chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

236 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Experimental

Arm Type

Experimental

Arm Description

Arm Title

Active Comparator

Arm Type

Active Comparator

Arm Description

IMRT and concurrent cisplatin Patients receive intensity modulated-radiotherapy (IMRT), concurrently with weekly cisplatin 40 mg/m² up to 7cycles.

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Intervention Description

Experimental arm: Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 2 cycles before IMRT.

Intervention Type

Drug

Intervention Name(s)

cisplatin

Other Intervention Name(s)

DDP

Intervention Description

Experimental arm: Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 2 cycles before IMRT.

Intervention Type

Drug

Intervention Name(s)

cisplatin

Other Intervention Name(s)

DDP

Intervention Description

Active Comparator arm: Patients receive weekly cisplatin 40 mg/m² up to 7cycles during IMRT.

Intervention Type

Radiation

Intervention Name(s)

Intensity-modulated Radiotherapy

Other Intervention Name(s)

IMRT

Intervention Description

Intensity modulated-radiotherapy (IMRT) is given as 2.0-2.33 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.

Primary Outcome Measure Information:

Title

Failure-free survival

Description

Failure-free survival rate is calculated from the date of randomization to the date of treatment failure or death from any cause, whichever is first.

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Overall survival

Description

Overall survival is calculated from randomization to death from any cause.

Time Frame

2 years

Title

Locoregional failure-free survival

Description

Locoregional failure-free survival is calculated from randomization to the first locoregional failure.

Time Frame

2 years

Title

Distant failure-free survival

Description

Distant failure-free survival is calculated from randomization to the first remote failure.

Time Frame

2 years

Title

Overall response rate

Description

Overall response rate at 3 months after completion of IMRT

Time Frame

3 months after completion of IMRT

Title

Number of participants with adverse events

Description

Incidence of acute and late toxicity

Time Frame

2 years

Title

Quality of life during treatment

Description

Quality of life is measured by FACIT questionnaire.

Time Frame

During whole chemotherapy and IMRT treatment.For experimental arm, an expected average of 12 weeks; for active comparator arm, an expected average of 6 weeks.

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 nasopharyngeal carcinoma (including WHO II or III). Tumor staged as T1-4N2-3或T3-4N0-1M0 (according to the 7th AJCC edition). Satisfactory performance status: Karnofsky scale (KPS) ≥ 70. Adequate marrow: leucocyte count ≥ 4000/μL, hemoglobin ≥ 90g/L and platelet count ≥ 100000/μL. Adequate liver function: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) < 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) ≤ 2.5×ULN, and bilirubin ≤1.5×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: WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pei-Yu Huang, M. D., Ph.D.

Organizational Affiliation

Sun Yat-sen University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sun Yat-sen University Cancer Center

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

12. IPD Sharing Statement

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The Role of Induction Gemcitabine and Cisplatin in Locoregionally Advanced Nasopharyngeal Carcinoma in the Era of IMRT

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