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

Nasopharyngeal Carcinoma Clinical Trial

Official title:

A Randomized Phase III Prospective Study of Induction Chemotherapy Combined With Concurrent Chemoradiotherapy Versus Induction Chemotherapy Combined With Radiotherapy Alone in Locoregionally Advanced Nasopharyngeal Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05527470
• Other study ID #: GLMU-08
• Status: Recruiting
• Phase: Phase 3
• Start date: November 11, 2022
• Est. completion date: November 11, 2027

Study information

• Verified date: April 2023
• Source: Guilin Medical University, China
• Contact: Wei Jiang, PhD
• Phone: +86-2882906
• Email: weijiang[@]glmc.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 440
• Est. completion date: November 11, 2027
• Est. primary completion date: November 11, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma

Intervention

Drug:
• Gemcitabine,Cisplatin
Induction chemotherapy: Patients receive 1000 mg/m2 gemcitabine intravenously on day 1and day 8, 80mg/m2 cisplatin intravenously on day 1 to 3, three cycles were administered at intervals of 3 weeks.

Radiation:
• Intensity-modulated radiation therapy (IMRT)
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.

Drug:
• Cisplatin
Concurrent chemotherapy: Patients received 100mg/m2 cisplatin intravenously on day 1 to 3, three cycles were administered at intervals of 3 weeks.

Locations

Country	Name	City	State
China	Affiliated Hospital of Guilin Medical University	Guilin	Guangxi
China	Wuzhou Red Cross Hospital	Wuzhou	Guangxi

Sponsors (6)

Lead Sponsor	Collaborator
Wei Jiang	Laibin People's Hospital, Lingshan people's Hospital, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Nationalities Hospital of Guangxi Zhuang Autonomous Region, Wuzhou Red Cross Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	Progression-free survival is from randomization to first disease progression [local recurrence and/or distant metastasis] or death from any cause	3 years
Secondary	Overall Survival	Overall survival is from randomization to death of any cause or last follow-up	3 years
Secondary	Locoregional Failure-free Survival	Locoregional failure-free survival is from randomization to locoregional progression	3 years
Secondary	Distant Failure-free Survival	Distant failure-free survival is from randomization to first distant metastasis	3 years
Secondary	Objective response rate	Objective response rate is the percentage of patients achieving complete response (CR) and partial response (PR) according to RECIST 1.1 criteria.	3 years
Secondary	Number of Participants with Adverse Events	Incidence of acute and late toxicity	3 years