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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Nasopharyngeal Cancer
• Intervention / Treatment: Drug: Nab paclitaxel

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TPX neoadjuvant chemotherapy +CCRT; Patients receive neoadjuvant chemotherapy with Nab-PTX (150/175/200/225/250 mg/m2, D1) , cisplatin (75 mg/m2, D1) and capecitabine (1000 mg/m2, BID, D1-14) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100 mg/m2) concurrent every three weeks during radiotherapy (D1, D22, D43 of RT)	Drug: Nab paclitaxel; Nab paclitaxel plus cisplatin and capecitabine as neoadjuvant chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Disease control rate	The proportion of patients with response and stable disease (SD) after treatment, including patients with CR, PR and SD.	3 months
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
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

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Study Chair: Su Li, MD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2021
• Primary Completion (Actual): December 31, 2022
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: April 12, 2021
• First Submitted That Met QC Criteria: April 18, 2021
• First Posted (Actual): April 20, 2021

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 19, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: 2020-FXY-489

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No