TPC Versus GP Induction Chemotherapy for Nasopharyngeal Carcinoma

TPC Versus GP Induction Chemotherapy Followed by Concurrent Chemoradiotherapy for High-risk Locoregionally Advanced Nasopharyngeal Carcinoma, a Multi-center Phase II Randomized Trial

The NCCN guidelines recommend induction chemotherapy followed by concurrent chemoradiotherapy as the standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, meta-analyses have shown significant survival differences between different induction chemotherapy regimens. How to choose an induction chemotherapy regimen and treatment course that ensures definitive therapeutic effects and low incidence of toxic side effects remains a hot spot in clinical research. Polymeric micellar paclitaxel are an innovative form of paclitaxel drugs, with high penetration and long retention effects, which can enter the vascularly disordered tumor microenvironment through passive targeting and form higher concentrations in tumor tissue. It remains to be investigated whether the TPC (paclitaxel, cisplatin and capecitabine) regimen based on polymeric micellar paclitaxel compared to the current standard first-line induction chemotherapy GP (gemcitabine, cisplatin) regimen can further improve therapeutic effects in high-risk patients with locally advanced disease. There is still a lack of head-to-head studies for comparison. This study aims to compare, through a prospective, parallel-controlled, randomized, open-label, multicenter phase II clinical trial, the TPC induction chemotherapy vs. the GP induction chemotherapy combined with concurrent chemoradiotherapy for the treatment of high-risk locoregionally advanced NPC (T4 or N2-3) in terms of 2-year progression-free survival, overall survival, overall response rate, toxic side effects, etc.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: TPC induction chemotherapy; Drug: GP induction chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 162
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hai-Qiang Mai; Phone Number: 086-020-8734; Email: maihq@sysucc.org.cn
• Study Contact Backup: Name: Mai; Phone Number: 086-020-8734; Email: maihq@sysucc.org.cn

Study Locations

• China
  • Dongguan, China
    • Not yet recruiting
    • Dongguan People's Hospital
    • Contact: Zhigang Liu
  • Foshan, China
    • Not yet recruiting
    • Foshan First People's Hospital
    • Contact: Ning Zhang
  • Shenzhen, China
    • Recruiting
    • Peking University Shenzhen Hospital
    • Contact: Yajie Liu, MD
  • Wuhan, China
    • Recruiting
    • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
    • Contact: Kunyu Yang
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Hai-Qiang Mai; Phone Number: 86-20-8734-364 860-020-8734; Email: maihq@sysucc.org.cn
      • Principal Investigator: Hai-Qiang Mai, MD,PhD
  • Please Select
    • Guangzhou, Please Select, China, 510060
      • Not yet recruiting
      • Affiliated Cancer Hospital and institute of Guangzhou Medical University
      • Contact: Weijun Zhang
    • Guangzhou, Please Select, China, 510060
      • Not yet recruiting
      • Sun Yat-Sen Memorial Hospital
      • Contact: Shoumin Bai
    • Guangzhou, Please Select, China, 510060
      • Not yet recruiting
      • The First Affiliated Hospital of Guangzhou Medical University
      • Contact: Jiancong Sun

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age between 18 and 65 years;
2. Pathologically confirmed differentiated non-keratinizing carcinoma and undifferentiated non-keratinizing carcinoma (WHO type II or III);
3. Staged as T4N0-3M0 or T1-4N2-3M0 (UICC 8th edition);
4. Easte Cooperative Oncology Group performance status of 0 or 1;
5. Adequate bone marrow: leucocyte count ≥ 4×109/L, hemoglobin ≥ 90g/L and platelet count ≥ 100×109/L;
6. Adequate hepatic function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) and AST or ALT ≤ 1.5 xULN;
7. Adequate renal function: creatinine clearance rate ≥ 60 ml/min or creatinine ≤ 1.5× ULN;
8. Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control throughout protocol treatment;
9. Patients must be appraised of the investigational nature of the study and provide written informed consent.

Exclusion Criteria:

1. WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma;
2. Treatment with palliative intent;
3. Prior malignancy (except for adequately treated carcinoma in situ of the cervix, or basal or squamous cell carcinoma of the skin);
4. History of previous radiotherapy (except for non-melanomatous skin cancers outside intended RT treatment volume);
5. Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes.
6. Pregnancy or lactation (consider pregnancy test in women of child-bearing age and emphasize effective contraception during the treatment period);
7. 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;
8. Prior allergic reaction to the study drug(s) involved in this protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TPC induction chemotherapy + CCRT; TPC induction chemotherapy regimen followed by concurrent chemoraditherapy (cisplatin 100 mg/m2, every 3 weeks for 3 cycles) and IMRT (PTVnx 70Gy/33f; PTVnd 70Gy/33f; PTV1 60Gy/33f; PTV2 54Gy/33f)	Drug: TPC induction chemotherapy; TPC induction chemotherapy regimen contains Polymeric micellar paclitaxel, which is a novel Cremophor EL-free, nanoparticle micellar formulation of paclitaxel, cisplatin and capecitabine. TPC induction chemotherapy regimen (polymeric micellar paclitaxel 200 mg/m2 D1, cisplatin 75 mg/m2 D1, capecitabine 1000 mg/m2/day D1-14, every 3 weeks for 3 cycles).
Active Comparator: GP induction chemotherapy + CCRT; GP induction chemotherapy regimen followed by concurrent chemoraditherapy (cisplatin 100 mg/m2, every 3 weeks for 3 cycles) and IMRT (PTVnx 70Gy/33f; PTVnd 70Gy/33f; PTV1 60Gy/33f; PTV2 54Gy/33f)	Drug: GP induction chemotherapy; GP induction chemotherapy regimen (gemcitabine 1000 mg/m2 D1/8, cisplatin 80 mg/m2 D1, every 3 weeks for 3 cycles)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Defined as the time from random assignment to documented local or regional relapse, distant metastasis, or death from any cause, whichever occurred first.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Defined as the time from random assignment to death from any cause.	2 years
Distant progression	Defined as the time from random assignment to the occurrence of a distant progression. Cumulative incidence of distant progression will be calculated within a competing risk framework (Fine and Gray 1999).	2 years
Locoregional progression	Defined as the time from random assignment to the occurrence of a locoregional progression. Cumulative incidence of locoregional progression will be calculated within a competing risk framework (Fine and Gray 1999).	2 years
Short-term response rate	Tumour response was classified according to RECIST, version 1.1	32 weeks
Incidence of acute and late toxicity	Incidence of acute toxicity is evaluated on basis of Common Terminology Criteria for Adverse Events (CTCAE) 5.0 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. Acute adverse events, occurring during study treatment, and radiation-related late adverse events, occurring from 3 months after completion of radiotherapy, and chemotherapy-induced late adverse events, occurring from 3 months after completion of chemotherapy until end of follow up).	2 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: February 24, 2024
• First Submitted That Met QC Criteria: March 6, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Actual): July 8, 2024
• Last Update Submitted That Met QC Criteria: July 4, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: GP; TPC; Polymeric micellar paclitaxel
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma
• Other Study ID Numbers: 2023-FXY-129

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No