TPC Versus GP Induction Chemotherapy for Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06301165
• Other study ID #: 2023-FXY-129
• Status: Recruiting
• Phase: Phase 2
• Start date: March 19, 2024
• Est. completion date: December 31, 2028

Study information

• Verified date: April 2024
• Source: Sun Yat-sen University
• Contact: Hai-Qiang Mai
• Phone: 086-020-8734
• Email: maihq[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 162
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma

Intervention

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).
• GP induction chemotherapy
GP induction chemotherapy regimen (gemcitabine 1000 mg/m2 D1/8, cisplatin 80 mg/m2 D1, every 3 weeks for 3 cycles)

Locations

Country	Name	City	State
China	Dongguan people's hospital	Dongguan
China	Foshan First People's Hospital	Foshan
China	Affiliated cancer hospital and institute of guangzhou medical university	Guangzhou	Please Select
China	Sun Yat-Sen Memorial Hospital	Guangzhou	Please Select
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Please Select
China	Peking university shenzhen hospital	Shenzhen
China	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall survival	Defined as the time from random assignment to death from any cause.	2 years
Secondary	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
Secondary	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
Secondary	Short-term response rate	Tumour response was classified according to RECIST, version 1.1	32 weeks
Secondary	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