Induction Chemotherapy Followed by IMRT or Concurrent Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma

Phase 3

Recruiting

• Conditions: Nasopharyngeal Carcinoma
• Interventions: Drug: Gemcitabine,Cisplatin; Radiation: Intensity-modulated radiation therapy (IMRT); Drug: Cisplatin

• Registration Number: NCT05527470
• Lead Sponsor: Wei Jiang

Brief Summary

In the era of comprehensive therapy, many studies have investigated the value of induction chemotherapy (IC) in the treatment of nasopharyngeal carcinoma (NPC). Concurrent cisplatin and radiotherapy is the foundation of concurrent chemoradiotherapy strategies, and the addition of cisplatin-based induction chemotherapy to concurrent chemoradiotherapy (CCRT) is considered to prolong survival by reducing distant metastasis in patients with high-risk disease. However, the severity of acute toxicities was significantly increased, which can compromise quality of life and lead to interruptions in CCRT. Fortunately, Locoregional control has substantially improved as the intensity-modulated radiation therapy (IMRT) technique has been widely used in the last decades, IMRT improved the treatment outcomes of patients with NPC, especially the local control rate. Currently, in the era of IMRT, whether patients with NPC benefit from IC plus radiotherapy alone and reduce toxicities compared with IC combined with CCRT. Therefore, the investigators propose this randomized phase III prospective study to assess the efficacy and contribution of IC plus radiotherapy alone in locoregionally advanced NPC during IMRT era.

Detailed Description

Patients with stage III-IVA (AJCC 8th, included T1-2N2-3 and/or T3-4N0-3 M0) locoregionally-advanced nasopharyngeal carcinoma will be randomized in a 1:1 ratio to experimental arm and active comparator arm. Patients in experimental arm will receive induction chemotherapy with gemcitabine (1g/m2, d1 \& 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. IMRT is given as 2.0-2.3 Gy per fraction with five daily fractions per week for 6-7 weeks, Cumulative doses were \> 66 Gy to the primary tumor and \> 50 Gy to the bilateral cervical lymph nodes and potential sites of local infiltration. Patients in active comparator arm will receive induction chemotherapy with gemcitabine (1g/m2, d1 \& 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. IMRT is given as 2.0-2.3 Gy per fraction with five daily fractions per week for 6-7 weeks, Cumulative doses were \> 66 Gy to the primary tumor and \> 50 Gy to the bilateral cervical lymph nodes and potential sites of local infiltration. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 3 cycles during IMRT.

Study Timeline

• Study First Submitted: 2022-08-30
• Study First Submitted QC: 2022-09-01
• Study First Posted: 2022-09-02
• Study Start: 2022-11-11
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-30
• Last Update Posted: 2023-05-03
• Primary Completion: 2025-11-11
• Study Completion: 2027-11-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 440

Inclusion Criteria

1. Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type);
2. Tumor staged as III-IVb (according to the 8th AJCC edition);
3. No pregnant female;
4. Age between 18-65;
5. Normal complete blood count level (hemoglobin >10 g/dL, white blood cells ≥4000/μL, platelets ≥100 000/μL);
6. Normal hepatic functions (serum total bilirubin ≤1.6 mg/dL, serum transminase < 2.5 times higher than upper limit);
7. Normal renal function (serum creatinine ≤1.5 mg/dL, creatinine clearance ≥60 mL/min);
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
9. Without radiotherapy or chemotherapy;
10. Patients must give signed informed consent.

Exclusion Criteria

1. Disease progression in the process of the treatment;
2. The presence of uncontrolled life-threatening illness;
3. History of previous radiotherapy or chemotherapy;
4. Pregnancy or lactation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Induction CT+IMRT Combined Concurrent CT	Gemcitabine,Cisplatin	Induction Chemotherapy(CT) Followed by Intensity-modulated Radiation Therapy (IMRT ) Combined Concurrent Chemotherapy
Induction CT+IMRT Combined Concurrent CT	Intensity-modulated radiation therapy (IMRT)	Induction Chemotherapy(CT) Followed by Intensity-modulated Radiation Therapy (IMRT ) Combined Concurrent Chemotherapy
Induction CT+IMRT alone	Gemcitabine,Cisplatin	Induction Chemotherapy(CT) Followed by Intensity-modulated Radiation Therapy (IMRT )alone
Induction CT+IMRT alone	Intensity-modulated radiation therapy (IMRT)	Induction Chemotherapy(CT) Followed by Intensity-modulated Radiation Therapy (IMRT )alone
Induction CT+IMRT Combined Concurrent CT	Cisplatin	Induction Chemotherapy(CT) Followed by Intensity-modulated Radiation Therapy (IMRT ) Combined Concurrent Chemotherapy

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	3 years	Progression-free survival is from randomization to first disease progression \[local recurrence and/or distant metastasis\] or death from any cause

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events	3 years	Incidence of acute and late toxicity
Distant Failure-free Survival	3 years	Distant failure-free survival is from randomization to first distant metastasis
Objective response rate	3 years	Objective response rate is the percentage of patients achieving complete response (CR) and partial response (PR) according to RECIST 1.1 criteria.
Overall Survival	3 years	Overall survival is from randomization to death of any cause or last follow-up
Locoregional Failure-free Survival	3 years	Locoregional failure-free survival is from randomization to locoregional progression

Trial Locations

Locations (2)

Affiliated Hospital of Guilin Medical University; 🇨🇳 Guilin, Guangxi, China

Wuzhou Red Cross Hospital; 🇨🇳 Wuzhou, Guangxi, China