A Study for Assessing the Efficacy and Safety of Tetrahydrobiopterin in Radiation-Induced Skin Injury

NCT05114226 | Unknown Phase 1

• 1 other identifier: WCSUH2021002
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This study was a single-center prospective phase I clinical study to evaluate the effectiveness and safety of BH4 in the treatment of radiation-induced skin injury during vulvar cancer radiotherapy.

Conditions

Radiation-Induced Dermatitis

Keywords

Tetrahydrobiopterin; Radiation-Induced Skin Injury; Phase I Clinical Study; Vulvar Cancer

Outcome Measures

Primary Outcomes (1)

• Acute radiation dermatitis incidence

  incidence that was evaluated every week (according to RTOG radiation morbidity scoring criteria)

  up to 12 weeks

Secondary Outcomes (3)

• progression-free survival (PFS)

  up to 5 years

• overall survival (OS)

  up to 5 years

• cancer remission rate assessed by imaging

  up to 12 weeks

Other Outcomes (1)

• adverse events

  up to 12 weeks

Study Arms (7)

experimental group (BH4 solvent 50 ug/ml)

EXPERIMENTAL

A sterile gauze was soaked with BH4 solvent (50 ug/ml), wringed out, and applied to the treated skin area for 15 minutes. It was applied three times a day (morning, noon, and evening), until three months after the end of treatment.

Drug: Tetrahydrobiopterin

experimental group (BH4 solvent 100 ug/ml)

EXPERIMENTAL

A sterile gauze was soaked with BH4 solvent (100 ug/ml), wringed out, and applied to the treated skin area for 15 minutes. It was applied three times a day (morning, noon, and evening), until three months after the end of treatment.

Drug: Tetrahydrobiopterin

experimental group（BH4 solvent 200 ug/ml)

EXPERIMENTAL

A sterile gauze was soaked with BH4 solvent (200 ug/ml), wringed out, and applied to the treated skin area for 15 minutes. It was applied three times a day (morning, noon, and evening), until three months after the end of treatment.

Drug: Tetrahydrobiopterin

experimental group（BH4 solvent 400 ug/ml)

EXPERIMENTAL

A sterile gauze was soaked with BH4 solvent (400 ug/ml), wringed out, and applied to the treated skin area for 15 minutes. It was applied three times a day (morning, noon, and evening), until three months after the end of treatment.

Drug: Tetrahydrobiopterin

experimental group（BH4 solvent 600 ug/ml)

EXPERIMENTAL

A sterile gauze was soaked with BH4 solvent (600 ug/ml), wringed out, and applied to the treated skin area for 15 minutes. It was applied three times a day (morning, noon, and evening), until three months after the end of treatment.

Drug: Tetrahydrobiopterin

experimental group（BH4 solvent 800 ug/ml)

EXPERIMENTAL

A sterile gauze was soaked with BH4 solvent (800 ug/ml), wringed out, and applied to the treated skin area for 15 minutes. It was applied three times a day (morning, noon, and evening), until three months after the end of treatment.

Drug: Tetrahydrobiopterin

experimental group（BH4 solvent 1000 ug/ml)

EXPERIMENTAL

A sterile gauze was soaked with BH4 solvent (1000 ug/ml), wringed out, and applied to the treated skin area for 15 minutes. It was applied three times a day (morning, noon, and evening), until three months after the end of treatment.

Drug: Tetrahydrobiopterin

Interventions

Tetrahydrobiopterin DRUG

BH4 was applied when skin damage≥ Grade I occurred. A sterile gauze was soaked with BH4 solvent, wringed out, and applied to the treated skin area for 15 minutes. It was applied three times a day (morning, noon, and evening), until three months after the end of treatment.

experimental group (BH4 solvent 100 ug/ml); experimental group (BH4 solvent 50 ug/ml); experimental group（BH4 solvent 1000 ug/ml); experimental group（BH4 solvent 200 ug/ml); experimental group（BH4 solvent 400 ug/ml); experimental group（BH4 solvent 600 ug/ml); experimental group（BH4 solvent 800 ug/ml)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: ≥ 18years old female patients.
• The subjects of the study were pathologically diagnosed vulvar cancer patients, who needed postoperative supplemental radiotherapy, patients who received radical radiotherapy and chemotherapy (unresectable locally advanced tumors, including some stage II with tumor diameter \> 4 cm or tumor invading vagina, urethra, and anus), and early-stage patients with possible serious postoperative complications or serious complications, where in the option of undergoing a surgery was not appropriate.
• The Eastern Cooperative Oncology GroupPerformance Status (ECOG PS) score: 0-1.
• Expected survival ≥12 months.
• The main organs functioned normally, which meant that they met the following criteria:
• \) Blood routine examination results:
• Hemoglobin (Hb) ≥90g/L. ② Absolute neutrophil count (ANC)≥1.5×109/L. ③ Platelet count (PLT) ≥50×109/L. 2) Biochemical examination results:
• Total bilirubin (TBIL)\<1.5×upper limit of normal (ULN).
• Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)\<2.5×ULN,for patients with liver metastasis\<5×ULN.
• ③ Blood urea nitrogen (BUN) and Creatinine ratio (CR) ≤1×ULN or Endogenous creatinine clearance≥50ml/min(by Cockcroft-Gault equation).
• \. The subjects willingly participated inthe study, signed an informed consent form, were medication-compliant, and cooperated with the follow-ups.

You may not qualify if:

• Patients with hypertension and could not control the blood pressure within the normal range after treating with antihypertensive medications (systolic blood pressure\>140 mmHg and diastolic blood pressure\>90 mmHg).
• Patients with a history of severe cardiovascular diseases, including myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmia (QTc interval ≥470 ms in women), grade III\~IV cardiac insufficiencyaccording to the New York Heart Association (NYHA) standards, orthe left ventricular ejection fraction (LVEF) \< 50%shown by the heart color Doppler ultrasound.
• Patients with coagulation disorders (international normalized ratio (INR) \>1.5, activated partial thromboplastin time (aPTT) \>1.5 ULN), with bleeding tendency.
• Patients with a history of psychotropic medication abuse and unable to quit, and patients with mental disorders.
• Patients participatingin another drug trial.
• Patients with concomitant diseases that seriously endangered the safety of the patient or affected the completion of the study from the investigators' opinion.
• Not suitable for enrollment in the investigators' opinion.

Sponsors & Collaborators

• West China Second University Hospital: lead

Study Sites (1)

est China Second Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

Location

Related Publications (1)

• Xue J, Yu C, Sheng W, Zhu W, Luo J, Zhang Q, Yang H, Cao H, Wang W, Zhou J, Wu J, Cao P, Chen M, Ding WQ, Cao J, Zhang S. The Nrf2/GCH1/BH4 Axis Ameliorates Radiation-Induced Skin Injury by Modulating the ROS Cascade. J Invest Dermatol. 2017 Oct;137(10):2059-2068. doi: 10.1016/j.jid.2017.05.019. Epub 2017 Jun 6.

  PMID: 28596000 RESULT

MeSH Terms

Conditions

Radiodermatitis; Vulvar Neoplasms

Interventions

sapropterin

Condition Hierarchy (Ancestors)

Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Radiation Injuries; Wounds and Injuries; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Vulvar Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Model Details: The degree of the skin injury during the radiotherapy was assessedaccording to the radiation morbidity scoring criteria of the Radiation Therapy Oncology Group (RTOG).After the start of radiotherapy, the degree of the damage to the patient's skin was assessed every week. BH4 was applied when skin damage≥ Grade I occurred. A sterile gauze was soaked with BH4 solvent, wringed out, and applied to the treated skin area for 15 minutes. It was applied three times a day (morning, noon, and evening), until three months after the end of treatment. BH4 gradient: 50, 100, 200, 400, 600, 800, and 1,000 ug/ml.

Study Record Dates

• First Submitted: October 12, 2021
• First Posted: November 9, 2021
• Study Start: March 1, 2022
• Primary Completion: November 1, 2023
• Study Completion: January 1, 2024
• Last Updated: February 28, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)