Chemoradiotherapy for Patients With Locally Advanced Nasopharyngeal Carcinoma Using Raltitrexed-Cisplatin

Study Of Induction Chemotherapy Followed by Concurrent Chemoradiotherapy With Raltitrexed-Cisplatin for Patients With Locally Advanced Nasopharyngeal Carcinoma

The purpose of this study is to evaluate the efficacy and safety of raltitrexed and cisplatin neoadjuvant chemotherapy followed by concurrent radiotherapy with raltitrexed and cisplatin in patients with locally advanced nasopharyngeal carcinoma.

Study Overview

• Status: Completed
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: raltitrexed-cisplatin; Radiation: Intensity-modulated radiotherapy (IMRT)

Detailed Description

Although concurrent chemoradiation is the standard treatment modality for locally advanced nasopharyngeal carcinoma (NPC), high incidences of distant metastases and severe treatment related toxicities have become an obstacle to be overcome. A phase Ⅱ study conducted by Hui et al. showed that neoadjuvant chemotherapy followed by concurrent chemoradiotherapy was superior to the standard concomitant chemoradiation in terms of the 3-year OS without significantly exacerbating the acute toxicities.

At present, PF regimen has been considered as the most classic chemotherapy regimen of nasopharyngeal carcinoma (NPC), but its efficiency is about 40%-60% , and always with severe gastrointestinal reactions, renal toxicity and oral mucosa reaction. Therefore, it is imperative to find a more safe and effective chemotherapy regimen.

Raltitrexed is a specific thymidylate synthase inhibitor with a convenient administration schedule,acceptable and manageable toxicity, radiosensitising properties. It may offer advantages compared with standard 5-FU chemotherapy regimens used in locally advanced NPC.

Therefore, the investigators initiated this study to evaluate the efficacy and safety of raltitrexed and cisplatin neoadjuvant chemotherapy followed by concurrent radiotherapy with raltitrexed and cisplatin in patients with locally advanced NPC.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with newly histologically confirmed nasopharyngeal carcinoma, including WHO III
2. Newly diagnosed T3-4 or any TN2-3 locally advanced nasopharyngeal carcinoma
3. At least one measurable lesion (according to the RECIST1.1)
4. female and male,18-70 years of age
5. ECOG performance status of 0-1
6. Life expectancy of more than 3 months
7. Without radiotherapy or chemotherapy

8. Adequate organ function including the following:

   Platelets count >= 100 * 109/l Absolute neutrophil count (ANC) >= 2.0 * 109/l Hemoglobin >= 90 g/l Total bilirubin <= 1.5ULN AST and ALT <= 2.5ULN,if there is liver metastasis , AST and ALT <= 5ULN Serum creatine <= 1.5ULN

9. Signed and dated informed consent.

Exclusion Criteria:

1. Before or at the same time any second malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
2. Evidence of distant metastasis
3. Taboos of chemotherapy or radiotherapy(such as heart failure, angina pectoris, or cardiac arrhythmia.et al) Presence of an uncontrolled concomitant illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
4. Pregnant or breast-feeding females
5. Abuse of psychiatric drugs or dysphrenia
6. Prior chemotherapy with raltitrexed or cisplatin
7. Allergic to clinical drugs
8. Participation in clinical trials for other anti-tumor drugs in 4 weeks
9. Evidence of significant medical illness that in the investigator's judgment will substantially increase the risk associated with the subject's participation in and completion of the study

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: drug:raltitrexed safety and efficacy; To receive the safety and efficacy of raltitrexed-cisplatin neoadjuvant chemotherapy followed by concurrent chemoradiotherapy with raltitrexed-cisplatin Interventions: Neochemotherapy (Induction Chemotherapy) Drugs: raltitrexed-cisplatin (Raltitrexed, 2.5mg/m2, IV in 15 minutes, d1; Cisplatin, 25mg/m2, IV, d1-3.Cycled every 21 days for 2 cycles). Concurrent Chemotherapy Drugs: raltitrexed-cisplatin (Raltitrexed, 2.5mg/m2, IV in 15 minutes, d1; Cisplatin, 25mg/m2, IV, d1-3.Cycled every 21 days for 2 cycles) . Radiation: Intensity-modulated radiotherapy (IMRT)

Drug: raltitrexed-cisplatin; Patients receive raltitrexed-cisplatin neoadjuvant chemotherapy every three weeks for two cycles, then receive raltitrexed -cisplatin concurrent chemoradiotherapy every three weeks for two cycles; Other Names: Tomudex; Radiation: Intensity-modulated radiotherapy (IMRT); Patients receive raltitrexed -cisplatin concurrent chemoradiotherapy every three weeks for two cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
ORR (Objective Response Rate)	up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
OS(Overall Survival)	2 years
TTP（Time To Progression）	2 years
DCR (Disease Control Rate)	6 weeks after induction chemotherapy; 4 weeks and 12 weeks after radiotherapy.
QOL（Quality Of Life）	2 years

Collaborators and Investigators

• Sponsor: Hubei Cancer Hospital
• Investigators: Principal Investigator: Desheng Hu, M.D., Associate dean

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: September 23, 2015
• First Submitted That Met QC Criteria: September 28, 2015
• First Posted (Estimate): September 29, 2015

Study Record Updates

• Last Update Posted (Actual): February 22, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Concurrent Chemoradiotherapy; Induction Chemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Folic Acid Antagonists; Cisplatin; Raltitrexed
• Other Study ID Numbers: Radiotherapy center-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There are not enough people participated in the treatment.