Clinical trial NCT04850235: Nab-paclitaxel Based TPX Neoadjuvant Chemotherapy for NPC Patients: a Dose-escalation Study
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Nasopharyngeal Cancer
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2021-04-20
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum tolerated dose
timeFrame: At the end of each cycle (each cycle is 21 days)
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: At the end of each cycle (each cycle is 21 days)
Secondary outcomes:
measure: Objective response rate
timeFrame: 3 months
measure: Disease control rate
timeFrame: 3 months
measure: Overall survival
timeFrame: 2-year
measure: Progression-free survival
timeFrame: 2-year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
References: