BH4 in the Prevention and Treatment of Radiation-induced Skin Reactions for Head and Neck Squamous Cell Carcinoma (Including Nasopharyngeal Carcinoma)

Sponsor

West China Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05299203

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Head and neck squamous cell carcinoma (include nasopharyngeal carcinoma) is one of the most common malignant tumor in China, and radiotherapy is the main treatment method. Radiation-induced dermatitis is one of the most common complications of head and neck squamous cell carcinoma patients during radiotherapy. Severe radiation dermatitis will cause secondary infection, severe pain, and even lead to the interruption of radiotherapy. On the one hand, it will affect the efficacy of tumor treatment, which may affect the long-term survival of patients, and on the other hand, it will also seriously affect the quality of life of patients. Tetrahydrobiopterin（BH4）, also known as sapropterin, has been shown not only to reduce the severity of acute radiation dermatitis but also to enhance the repair of skin injury in animal experiments. It may be a new approach and method for the prevention and treatment of radiation-induced dermatitis

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Squamous Cell Carcinoma	Drug: Sapropterin dihydrochloride tablets	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Phase Ia/Ib Clinical Trial of Sapropterin Dihydrochloride Tablets in the Prevention and Treatment of Radiation-induced Skin Reactions in Intensity Modulated Radiotherapy for Head and Neck Squamous Cell Carcinoma (Including Nasopharyngeal Carcinoma)

Anticipated Study Start Date :

May 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

May 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation and Expansion In the dose escalation phase, 9 patients will be included in 3 groups with 3 patients as one group. In the dose expansion phase, the concentration of Sapropterin dihydrochloride tablets (BH4) aqueous solution will be performed according to the effective concentration of dose escalation phase, and 9 patients will be enrolled.	Drug: Sapropterin dihydrochloride tablets dose escalation phase (BH4) aqueous solution is sprayed onto the skin of all radiotherapy areas, 3 times a day until two weeks after the end of radiotherapy.

Arm

Intervention/Treatment

Experimental: Dose Escalation and Expansion

In the dose escalation phase, 9 patients will be included in 3 groups with 3 patients as one group. In the dose expansion phase, the concentration of Sapropterin dihydrochloride tablets (BH4) aqueous solution will be performed according to the effective concentration of dose escalation phase, and 9 patients will be enrolled.

Drug: Sapropterin dihydrochloride tablets

dose escalation phase (BH4) aqueous solution is sprayed onto the skin of all radiotherapy areas, 3 times a day until two weeks after the end of radiotherapy.

Outcome Measures

Primary Outcome Measures

Radiation dermatitis grading change from the baseline to the 4 weeks after radiotherapy [Assessment is performed two weeks before radiotherapy, once a week during radiotherapy, the day at the end of radiotherapy, once a week for 4 weeks after radiotherapy.]
Radiation dermatitis is assessed according to the CTCAE 5.0 radiation dermatitis grading scale

Secondary Outcome Measures

Subjects' quality of life score change from the baseline to the 4 weeks after radiotherapy [Assessment is performed two weeks before radiotherapy, the day at the end of radiotherapy, 2 weeks after radiotherapy, 4 weeks after radiotherapy.]
Subjects' quality of life is assessed according to the Spitzer Quality-of-Life Index (SQLI)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed diagnosis of head and neck squamous cell carcinoma (including nasopharyngeal carcinoma).
Age ≥ 18 years old, ≤ 80 years old.
Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
Head and neck radiotherapy alone or concurrent chemoradiotherapy, radiotherapy using intensity modulated radiotherapy.
Blood routine examination: hemoglobin ≥ 100g/L, platelet count ≥ 75×10^{9/L, white
blood cell count ≥ 3.0×10}9/L, absolute neutrophil count ≥ 1.5×10^9/L. Blood biochemistry: total bilirubin≤1.5 upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5 ULN, serum creatinine ≤1.5 ULN or creatinine clearance rate >=60ml/min.
Have signed informed consent form.

Exclusion Criteria:

Allergic to the components of Sapropterin dihydrochloride tablets or severe allergic constitution.
Poor compliance.
Pregnant or breastfeeding.
Any previous radiotherapy to the head and neck region.
Patients deemed unsuitable for the study by the investigator (concomitant with any other serious disease)