Single-agent Capecitabine as Metronomic Chemotherapy in LAHNSCC (CMHN)

Single-agent Capecitabine as Metronomic Chemotherapy in Locoregionally Advanced Head and Neck Squamous Cell Carcinoma (CMHN)：A Phase III, Multicentre, Randomised Controlled Trial

The purpose of this study is to investigate whether the addition of metronomic capecitabine to the standard treatment can improve prognosis in locoregionally advanced head and neck squamous cell carcinoma.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Capecitabine

Detailed Description

The standard treatment for resectable locoregionally advanced squamous cell carcinoma of the head and the neck (LAHNSCC) is a regimen consisting of radical surgery plus radiotherapy or concurrent chemoradiotherapy. And induction chemotherapy plus radical radiotherapy or concurrent chemoradiotherapy is also recommended for locoregionally advanced squamous cell carcinoma of larynx and hypopharynx. With the extensive application of comprehensive treatment, the 5-year overall survival of LAHNSCC has not reached 50% yet. So, it is urgent to explore a regimen with high efficiency and low toxicity on the basis of existing standard treatment.

Two retrospective studies found that the metronomic use of orally administered fluorouracil drugs following the reference treatment significantly improved prognosis in LAHNSCC. And capecitabine is one kind of the oral fluorouracil drugs, which has high efficiency and low toxicity. Indeed, metronomic capecitabine maintenance was shown to be effective in patients with breast cancer, colorectal cancer, and nasopharyngeal carcinoma in phase III trials.

The abovementioned studies suggested the promising use of metronomic capecitabine in LAHNSCC. However, there has been no randomized trials in this field. Therefore, we initiated a randomized phase III trial to investigate the efficacy and safety of the addition of metronomic capecitabine to the standard treatment in LAHNSCC.

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ying Sun, M.D.; Phone Number: +86-(020)-87343816; Email: sunying@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Ying Sun, M.D.; Phone Number: +86-(020)-87343816; Email: sunying@sysucc.org.cn

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. Performance status of ECOG grade 0 or 1.
2. Tumor staged as III-IV (as defined by the 8th AJCC edition), with newly histologically confirmed squamous cell carcinoma of oral cavity, oropharynx, larynx or hypopharynx.

3. Complete one of the following treatments:

   1. Radical surgery plus radiotherapy or concurrent chemoradiotherapy
   2. Neoadjuvant therapy plus radical radiotherapy or concurrent chemoradiotherapy
   3. Concurrent chemoradiotherapy
4. Postoperative radiotherapy started within 4 to 8 weeks after completion of radical surgery.
5. Within 4 to 8 weeks after completion of the last radiation dose.
6. No clinical evidence of persistent locoregional disease or distant metastases before enrollment.
7. Adequate hematologic (neutrophil count > 1.5×10^9/L, hemoglobin > 90g/L and platelet count > 100×10^9/L), hepatic (alanine aminotransferase, aspartate aminotransferase ≤ 1.5×ULN, bilirubin ≤ 1.5×ULN, alkaline phosphatase ≤ 2.5×ULN) and renal function (creatinine clearance ≥ 50 ml/min).
8. Patients must be appraised of the investigational nature of the study and provide written informed consent.

Exclusion Criteria:

1. p16 positive.
2. Patients who were known to be intolerable or allergic to capecitabine.
3. Illness that would interfere with oral medication, including dysphagia, chronic diarrhea, or ileus.
4. Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer.
5. Pregnancy or lactation (consider pregnancy test in women of child-bearing age and emphasize effective contraception during the treatment period).
6. Prior surgery, chemotherapy, radiotherapy or other anti-tumor treatments (except diagnostic) to primary tumor or nodes before the standard therapy.
7. Patients who received surgery treatment, biotherapy or immunotherapy during radiotherapy.
8. Patients who are receiving or highly likely to receive other chemotherapy treatment, biotherapy or immunotherapy after radiotherapy.
9. Any severe intercurrent disease, which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control (fasting plasma glucose > 1.5×ULN), and emotional disturbance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Clinical observation; The standard treatment followed by clinical observation.
Experimental: Metronomic capecitabine; The standard treatment followed by a maintenance therapy with capecitabine (650 mg/m2 bid, d1-21, q3w) for 1 year.	Drug: Capecitabine; Metronomic capecitabine (650 mg/m2 bid, d1-21, q3w) for 1 year

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	PFS will be measured from the day of randomization until treatment failure, death from any cause, or the last follow-up visit, whichever occurred first.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	OS will be measured from the day of randomization until death due to any cause, or the last follow-up visit.	2 years
Distant failure-free survival	DFFS will be measured from the day of randomization until death until distant metastasis, or the last follow-up visit.	2 years
Locoregional failure-free survival	LRFFS will be measured from the day of randomization until death until local and/or regional recurrence, or the last follow-up visit.	2 years
Adverse events	The incidence of capecitabine-related and other adverse events.	Up to 2 years
Patient reported quality-of-life score	Patient reported quality of life would be evaluated using the Quality of Life Questionnaire-Core 30 module (QLQ-C30). The score is between 0-100, and the higher score means worse quality of life.	Up to 2 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Fujian Medical University Union Hospital; Yichang Central People's Hospital; The Affiliated Hospital of Guangdong Medical College; Jiangmen Central Hospital; Guangzhou Panyu Central Hospital; The Central Hospital of Yongzhou; The First People's Hospital of Huaihua; Hanzhong Central Hospital; Xiang Yang No.1 Peoples Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2021
• Primary Completion (Anticipated): October 1, 2026
• Study Completion (Anticipated): October 1, 2026

Study Registration Dates

• First Submitted: September 4, 2021
• First Submitted That Met QC Criteria: September 4, 2021
• First Posted (Actual): September 14, 2021

Study Record Updates

• Last Update Posted (Actual): March 3, 2022
• Last Update Submitted That Met QC Criteria: February 15, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: head and neck squamous cell carcinoma; metronomic capecitabine; locoregionally advanced disease
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: CMHN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No