Back to results

TPF+CCRT vs.CCRT+PF in High Risk Nasopharyngeal Carcinoma

Primary Purpose

Nasopharyngeal Carcinoma

Status

Active

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

TPF+CCRT

CCRT+ PF

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 carcinoma (according to World Health Organization (WHO) histologically type).
Original clinical staged as anyT N2-3M0（according to the American Joint Committee on Cancer(AJCC) 7th edition）and plasma EBVDNA≥1500copies/ml
No evidence of distant metastasis (M0).
Age 18-65 years old.
ECOG Performance status less or equal to 1
Adequate marrow: leucocyte count ≥4000/μL, hemoglobin ≥90g/L 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:

WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma.
Age <18 or >65years.
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

Sun Yat-sen Universitty Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

TPF+CCRT

CCRT+ PF

Arm Description

Patients receive induction chemotherapy with paclitaxel liposome (135mg/m2 on day 1) ,cisplatin (25mg/m2 on day 1-3) and 5-fluorouracil (750mg/m2 civ 120h) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100mg/m2) concurrent every three weeks during radiotherapy (D1,D22,D43 of RT) .

Patients receive concurrent IMRT and cisplatin (100mg/m2) concurrent every three weeks during radiotherapy (D1,D22,D43 of RT) , then followed by three cycles of adjuvant chemotherapy with cisplatin (80mg/m2 on day 1) and 5-fluorouracil (1000mg/m2 civ 96h) every four weeks for three cycles four weeks after radiotherapy.

Outcomes

Primary Outcome Measures

Progress-free survival(PFS)

Progress-free survival is calculated from the date of randomization to the date of the first progress at any site or death from any cause or censored at the date of the last follow-up.

Secondary Outcome Measures

Overall survival(OS)

The OS was defined as the duration from the date of random assignment to the date of death from any cause or censored at the date of the last follow-up.

Locoregional failure-free survival(LRRFS)

The LRRFS is evaluated and calculated from the date of random assignment until the day of first locoregional relapse or until the date of the last follow-up visit.

Distant metastasis-free survival(DMFS)

The DMFS is evaluated and calculated from the date of random assignment until the day of first distant metastases or until the date of the last follow-up visit.

Overall response rate

Tumour response was classified according to RECIST, version 1.1

Incidence of acute and late toxicity

Incidence of acute toxicity is calculated for each adverse event respectively and severity is evaluated on basis of Common Terminology Criteria for Adverse Events (CTCAE) 4.0 criteria.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.

Full Information

NCT ID

NCT03306121

First Posted

October 1, 2017

Last Updated

May 19, 2023

Sponsor

Sun Yat-sen University

1. Study Identification

Unique Protocol Identification Number

NCT03306121

Brief Title

TPF+CCRT vs.CCRT+PF in High Risk Nasopharyngeal Carcinoma

Official Title

Phase Ⅲ Trial of Induction Chemotherapy（TPF） Followed by Concurrent Chemoradiotherapy Versus Concurrent Chemoradiotherapy Followed by Adjuvant Chemotherapy (PF) in Patients With High Risk Nasopharyngeal Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

November 13, 2017 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2026 (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

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

To see the effect of induction chemotherapy（TPF） followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy (PF) in treating patients with high risk nasopharyngeal carcinoma (NPC).

Detailed Description

Patients presented with non-keratinizing NPC and stage AnyTN2-3M0 and plasma EBV DNA≥1500copies/ml are randomly assigned to receive TPF(paclitaxel liposome+cisplatin+5-fluorouracil) induction chemotherapy plus concurrent chemoradiotherapy (investigational arm) or concurrent chemoradiotherapy plus PF (cisplatin+5-fluorouracil) adjuvant chemotherapy (control arm). Patients in both arms receive intensity-modulated radiotherapy(IMRT), and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy. Patients in the investigational arm receive paclitaxel liposome (135mg/m2 on day 1), cisplatin (25mg/m2 on day 1-3) and 5-fluorouracil (750mg/m2 civ 120h) every three weeks for three cycles before the radiotherapy. Patients in the control arm receive adjuvant cisplatin (80mg/m2 on day 1) and 5-fluorouracil (1000mg/m2 civ 96h) every four weeks for three cycles after the radiotherapy. The primary end point is progress-free survival (PFS). Secondary end points include overall survival(OS),locoregional failure-free survival(LRRFS), distant metastasis-free survival(DMFS), overall response rates after treatments and toxic effects(short-term and long-term). All efficacy analyses are conducted in the intention-to-treat population.

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

322 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

TPF+CCRT

Arm Type

Experimental

Arm Description

Arm Title

CCRT+ PF

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

TPF+CCRT

Other Intervention Name(s)

TPF induction chemotherapy

Intervention Description

Patients receive paclitaxel liposome (135mg/m2 on day 1) , cisplatin (25mg/m2 on day 1-3) and 5-fluorouracil (750mg/m2 civ 120h) every three weeks for three cycles of induction chemotherapy before radiotherapy. Patients receive IMRT and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy (D1,D22,D43 of RT)

Intervention Type

Drug

Intervention Name(s)

CCRT+ PF

Other Intervention Name(s)

Adjuvant PF

Intervention Description

Patients receive cisplatin (80mg/m2 on day 1) and 5-fluorouracil (1000mg/m2 civ 96h) every four weeks for three cycles 4 weeks after radiotherapy. Patients receive IMRT and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy (D1,D22,D43 of RT)

Primary Outcome Measure Information:

Title

Progress-free survival(PFS)

Description

Progress-free survival is calculated from the date of randomization to the date of the first progress at any site or death from any cause or censored at the date of the last follow-up.

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Overall survival(OS)

Description

The OS was defined as the duration from the date of random assignment to the date of death from any cause or censored at the date of the last follow-up.

Time Frame

3 years

Title

Locoregional failure-free survival(LRRFS)

Description

The LRRFS is evaluated and calculated from the date of random assignment until the day of first locoregional relapse or until the date of the last follow-up visit.

Time Frame

3 years

Title

Distant metastasis-free survival(DMFS)

Description

The DMFS is evaluated and calculated from the date of random assignment until the day of first distant metastases or until the date of the last follow-up visit.

Time Frame

3 years

Title

Overall response rate

Description

Tumour response was classified according to RECIST, version 1.1

Time Frame

16 weeks after completion of IMRT

Title

Incidence of acute and late toxicity

Description

Time Frame

3 years

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 carcinoma (according to World Health Organization (WHO) histologically type). Original clinical staged as anyT N2-3M0（according to the American Joint Committee on Cancer(AJCC) 7th edition）and plasma EBVDNA≥1500copies/ml No evidence of distant metastasis (M0). Age 18-65 years old. ECOG Performance status less or equal to 1 Adequate marrow: leucocyte count ≥4000/μL, hemoglobin ≥90g/L 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: WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma. Age <18 or >65years. 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 Universitty Cancer Center

Official's Role

Study Chair

Facility Information:

Facility Name

Sun Yat-sen Universitty Cancer Center

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

9552031

Citation

Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley JF. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998 Apr;16(4):1310-7. doi: 10.1200/JCO.1998.16.4.1310.

Results Reference

result

PubMed Identifier

21112774

Citation

Lee AW, Tung SY, Ngan RK, Chappell R, Chua DT, Lu TX, Siu L, Tan T, Chan LK, Ng WT, Leung TW, Fu YT, Au GK, Zhao C, O'Sullivan B, Tan EH, Lau WH. Factors contributing to the efficacy of concurrent-adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma: combined analyses of NPC-9901 and NPC-9902 Trials. Eur J Cancer. 2011 Mar;47(5):656-66. doi: 10.1016/j.ejca.2010.10.026. Epub 2010 Nov 26.

Results Reference

result

PubMed Identifier

25957714

Citation

Blanchard P, Lee A, Marguet S, Leclercq J, Ng WT, Ma J, Chan AT, Huang PY, Benhamou E, Zhu G, Chua DT, Chen Y, Mai HQ, Kwong DL, Cheah SL, Moon J, Tung Y, Chi KH, Fountzilas G, Zhang L, Hui EP, Lu TX, Bourhis J, Pignon JP; MAC-NPC Collaborative Group. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol. 2015 Jun;16(6):645-55. doi: 10.1016/S1470-2045(15)70126-9. Epub 2015 May 6.

Results Reference

result

PubMed Identifier

27686945

Citation

Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, Chen XZ, Li JG, Zhu XD, Hu CS, Xu XY, Chen YY, Hu WH, Guo L, Mo HY, Chen L, Mao YP, Sun R, Ai P, Liang SB, Long GX, Zheng BM, Feng XL, Gong XC, Li L, Shen CY, Xu JY, Guo Y, Chen YM, Zhang F, Lin L, Tang LL, Liu MZ, Ma J. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016 Nov;17(11):1509-1520. doi: 10.1016/S1470-2045(16)30410-7. Epub 2016 Sep 27.

Results Reference

result

PubMed Identifier

23143190

Citation

Chen C, Wang FH, An X, Luo HY, Wang ZQ, Liang Y, Zhang L, Li YH. Triplet combination with paclitaxel, cisplatin and 5-FU is effective in metastatic and/or recurrent nasopharyngeal carcinoma. Cancer Chemother Pharmacol. 2013 Feb;71(2):371-8. doi: 10.1007/s00280-012-2020-x. Epub 2012 Nov 10.

Results Reference

result

Learn more about this trial

TPF+CCRT vs.CCRT+PF in High Risk Nasopharyngeal Carcinoma

We'll reach out to this number within 24 hrs