Nab-paclitaxel Based TPX Neoadjuvant Chemotherapy for NPC Patients: a Dose-escalation Study

Nasopharyngeal Cancer Clinical Trial

Official title:

Nab-paclitaxel Plus Cisplatin and Capecitabine as Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiation for Locoregionally Advanced Nasopharyngeal Carcinoma: a Phase I Dose-escalation Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04850235
• Other study ID #: 2020-FXY-489
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: April 15, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2023
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Neoadjuvant chemotherapy followed by concurrent chemoradiation (CCRT) has been recommended in the treatment of locoregionally-advanced nasopharyngeal carcinoma (NPC), with docetaxel, cisplatin (DDP) and 5-fluorouracil (5-Fu) shown to be an effective regimen. Capecitabine is the precursor drug of 5-fluorouracil, and has been used in replace of 5-fluorouracil in NPC patients. Nab-paclitaxel (Nab-PTX) is a novel albumin-bound paclitaxel with a superior therapeutic index to docetaxel. We sought to find out the efficacy of Nab-PTX in three-drug triplet (Nab-PTX, DDP and capecitabine) and decide the best administration dose of Nab-PTX.

Description:

Neoadjuvant chemotherapy followed by concurrent chemoradiation (CCRT) has been recommended in the treatment of locoregionally-advanced nasopharyngeal carcinoma (NPC), with docetaxel, cisplatin (DDP) and 5-fluorouracil (5-Fu) shown to be an effective regimen. Capecitabine is the precursor drug of 5-fluorouracil, and has been used in replace of 5-fluorouracil in NPC patients. Nab-paclitaxel (Nab-PTX) is a novel albumin-bound paclitaxel with a superior therapeutic index to docetaxel. It was developed to reduce toxicities associated with paclitaxel whilst maintaining or improving its chemotherapeutic effect. In vivo preclinical experiments have shown greater volume of distribution of nab-paclitaxel than paclitaxel, with similar half-life and clearance. The efficacy and optimal dose of Nab-PTX combined with DDP as doublet has been explored in metastatic NPC patients and locoregionally advanced patients, and it showed encouraging anti-tumor effects and manageable toxicities. However, what is the optimal dose of Nab-PTX and the efficacy of it in three-drug triplet (Nab-PTX, DDP and capecitabine) needs to be discovered. Therefore, this study aims to evaluate the efficacy and safety of Nab-PTX plus cisplatin and capecitabine neoadjuvant chemotherapy, followed by cisplatin-based concurrent chemoradiotherapy in the patients with locoregionally advanced nasopharyngeal carcinoma, to provide new evidence for the use of Nab-PTX in NPC.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma, including WHO II or III.

2. Original clinical staged as III-IVa (according to the 8th AJCC edition).

3. No evidence of distant metastasis (M0).

4. Male and no pregnant female.

5. Satisfactory performance status: ECOG (Eastern Cooperative OncologyGroup) scale 0-1.

6. WBC = 4×109 /L and PLT =100×109 /L and HGB =90 g/L.

7. With normal liver function test (ALT/AST = 2.5×ULN, TBIL= 2.0×ULN).

8. With normal renal function test (Creatinine Clearance = 60 ml/min ).

Exclusion Criteria:

1. Patients have evidence of relapse or distant metastasis.

2. Histologically confirmed keratinizing squamous cell carcinoma (WHO I).

3. Receiving radiotherapy or chemotherapy previously.

4. The presence of uncontrolled life-threatening illness.

5. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.

6. Receiving other ways of anti-cancer therapy.

7. Suffered from other malignant tumors (except the cure of basal cell carcinoma or uterine cervical carcinoma in situ) previously.

Related Conditions & MeSH terms

• Nasopharyngeal Cancer
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms

Intervention

Drug:
• Nab paclitaxel
Nab paclitaxel plus cisplatin and capecitabine as neoadjuvant chemotherapy

Locations

Country	Name	City	State
China	Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

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	Maximum tolerated dose	If more than one-third of patients in a given cohort experienced a dose-limiting toxicity (DLT), enrollment will be stopped and the dose used in the previous cohort will be designated as the maximum tolerated dose	At the end of each cycle (each cycle is 21 days)
Primary	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Incidence rate of adverse events (AEs), evaluated on basis of Common Terminology Criteria for Adverse Events (CTCAE) 5.0 criteria.	At the end of each cycle (each cycle is 21 days)
Secondary	Objective response rate	The proportion of patients whose tumors shrink to a certain size and maintain such size for a certain period of time, including patients with complete response (CR) and partial response (PR).	3 months
Secondary	Disease control rate	The proportion of patients with response and stable disease (SD) after treatment, including patients with CR, PR and SD.	3 months
Secondary	Overall survival	Overall survival is calculated from the date of enrollment to the date of the death from any cause or censored at the date of the last follow-up.	2-year
Secondary	Progression-free survival	Progress-free survival is calculated from the date of enrollment to the date of the first progression at any site or death from any cause or censored at the date of the last follow-up.	2-year