Safety and Superiority of Penicillamine in Radiosensitization of Recurrent Head and Neck Cancer

Head and Neck Cancer Clinical Trial

Official title:

Safety and Superiority of Penicillamine in Radiosensitization of Recurrent Head and Neck Cancer: a Single-center, Single-arm, Phase II Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06103617
• Other study ID #: NFEC-2023-416
• Status: Recruiting
• Phase: Phase 2
• Start date: November 15, 2023
• Est. completion date: June 1, 2025

Study information

• Verified date: November 2023
• Source: Nanfang Hospital, Southern Medical University
• Contact: Jian Guan, M.D
• Phone: +86-1363210224
• Email: 51643930[@]qq.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Our preclinical study confirmed that copper accumulation can lead to radioresistance in vitro and in vivo, and reducing the concentration of copper with copper chelator help to overcome radioresistance. Therefore, the investigators plan to carry out a prospective interventional phase II clinical trial to explore the safety and efficacy of penicillamine (a common copper chelator) as a radiosensitizer in the treatment of recurrent head and neck cancer.

Description:

Head and neck cancer is the sixth most common cancer worldwide. Radiotherapy is an important measure to control tumor recurrence. Although radiotherapy has been widely used in patients with head and neck cancer, the 2-year local recurrence rate of patients with locally advanced disease is still as high as 50%-60%. This is associated with a lower radiosensitivity in head and neck cancer. High doses of reirradiation (>60 Gy) are associated with severe late complications and treatment-related mortality. Therefore, finding an appropriate sensitizer to improve the radiosensitivity is the key to improve the survival of recurrent patients. Our preclinical study confirmed that copper accumulation can lead to radioresistance in vitro and in vivo, and the results were published in J Hepatol (IF=25.7). Penicillamine is a commonly used copper chelator in clinical practice and can reduce the concentration of copper in the body. Based on this, the investigators plan to carry out a prospective interventional phase II clinical trial to explore the safety and efficacy of penicillamine as a radiosensitizer in the treatment of recurrent head and neck cancer.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: June 1, 2025
• Est. primary completion date: October 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Sign informed consent

2. The age is 18-75 years

3. Previously received standard radical radiotherapy or chemoradiotherapy

4. Head and neck tumors with in situ or cervical lymph node recurrence confirmed by pathological biopsy and imaging examination

5. ECOG PS:0/1

6. Laboratory examination confirmed good organ function, which should be carried out within 10 days before the first treatment.

Exclusion Criteria:

1. After evaluation, it does not meet the indications of re-radiotherapy

2. Unable to take oral medication

3. Pregnancy or lactation

4. Known allergy to penicillamine

5. Patients who are judged by the researcher as unsuitable to participate in this trial.

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms
• Recurrence
• Recurrent Cancer

Intervention

Drug:
• Penicillamine
Participants in this group are treated with Penicillamine (250mg each time, 4 times per day) during reradiation.

Locations

Country	Name	City	State
China	Nanfang Hospital, Sourthern Medical University	Guangzhou
China	Southern medical university	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Nanfang Hospital, Southern Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	the biomarkers correlated with ORR, LRFS and OS	The correlations between ORR, OS, LRFS and PD-L1 expression in tissues, tumor mutation burden, tumor-related gene changes, plasma cytokines or other biomarkers were explored.	2 years
Primary	Objective response rate (ORR)	The objective response rate (ORR) is the proportion of patients who achieve a prespecified reduction in tumor volume that is maintained for a minimum duration. The objective response rate was defined as the sum of complete response plus partial response (CR+PR). According to RECIST1.1 criteria, CR was defined as the disappearance of target lesions and the reduction of the short diameter of pathological lymph nodes to less than 10mm. PR: the sum of the measured diameters of the target lesions reduced by 30% compared with the baseline; PD: the sum of the major diameters of all target lesions increased by at least 20%, and the absolute value of the sum of the major diameters increased by more than 5mm, or new lesions appeared. SD: Changes between PR and PD.	1 month
Secondary	Overall survival (OS)	OS was defined as the time from the date of inclusion until death from any cause.	2 years
Secondary	local-relapse free survival (LRFS)	LRFS was defined as the time from the date of inclusion until tumor relapse.	2 years
Secondary	Incidence of Treatment-Emergent Adverse Events	treatment-related adverse events will be assessed by CTCAE v5.0	During treatment and 12 weeks after penicillamine treatment