Concurrent Chemotherapy in Intermediate Risk Patients Treated With Intensity-modulated Radiotherapy

Sponsor

Sun Yat-sen University (Other)

Overall Status

Withdrawn

CT.gov ID

NCT02289807

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

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. hus, we 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, we decide to adopt the concurrent regimen to be cisplatin 100 mg/m2 on day 1, 22, 43

Condition or Disease	Intervention/Treatment	Phase
Nasopharyngeal Carcinoma	Drug: Cisplatin Radiation: IMRT	N/A

Detailed Description

Patients Patients with non-keratinizing NPC T1-2N1M0/T2-3N0M0 (UICC/AJCC 7th edition) are randomly assigned to receive CCRT or RT alone. Patients in CCRT group receive cisplatin 100 mg/m² every 3 weeks for 3 cycles, concurrently with intensity-modulated radiotherapy (IMRT). 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. 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Mar 1, 2015

Actual Primary Completion Date :

Aug 1, 2020

Anticipated Study Completion Date :

Aug 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RT group intensity modulated-radiotherapy (IMRT) alone Patients receive intensity modulated-radiotherapy (IMRT) alone	Radiation: IMRT 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
Active Comparator: CCRT group IMRT and concurrent cisplatin Patients receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles	Drug: Cisplatin concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles during IMRT Radiation: IMRT 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

Arm

Intervention/Treatment

Experimental: RT group

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

Radiation: IMRT

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

Active Comparator: CCRT group

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

Drug: Cisplatin

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

Radiation: IMRT

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

Outcome Measures

Primary Outcome Measures

Failure-free survival [3 Year]
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 [3 Year]
Overall survival is calculated from randomization to death from any cause
Locoregional failure-free survival [3 Year]
Locoregional failure-free survival is calculated from randomization to the first locoregional failure.
Distant failure-free survival [3 Year]
Distant failure-free survival is calculated from randomization to the first remote failure.
Number of participants with adverse events [3 Year]
Incidence of acute and late toxicity

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts 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 ≥ 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:

Neck lymph node with extracapsular spread. Maximal axial diameter of neck lymph node ≥30mm, positive neck lymph node at level IV and/or Vb.

Pretherapy plasma EBV DNA level ≥4000 copy/ml. WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma.

Age > 70 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.