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

NCT ID: NCT04850235

Last Updated: 2023-06-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-15
• Study Completion Date: 2024-12-31

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.

Conditions

Nasopharyngeal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

Nab paclitaxel

Intervention Type: DRUG

Nab paclitaxel plus cisplatin and capecitabine as neoadjuvant chemotherapy

Interventions

Nab paclitaxel

Nab paclitaxel plus cisplatin and capecitabine as neoadjuvant chemotherapy

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Hai-Qiang Mai,MD,PhD

Director of the Department of Nasopharyngeal Carcinoma

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Countries

China

References

Yu-Chen, Luo MJ, Liu RP, Jin J, Deng SW, Tang LQ, Li XY, Liu LT, Luo DH, Sun R, Liu SL, Li JB, Liu Q, Wang P, Chen QY, Mai HQ, Guo SS. Phase I dose-escalation study of nab-paclitaxel combined with cisplatin and capecitabin as induction chemotherapy followed by concurrent chemoradiotherapy in patients with nasopharyngeal carcinoma. Radiother Oncol. 2024 Feb;191:110051. doi: 10.1016/j.radonc.2023.110051. Epub 2023 Dec 21.

Reference Type: DERIVED

PMID: 38135184 (View on PubMed)

Other Identifiers

2020-FXY-489

Identifier Type: -

Identifier Source: org_study_id