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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Head and Neck Cancer, Recurrent Cancer

Intervention / Treatment
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* Drug: Penicillamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign informed consent The age is 18-75 years Previously received standard radical radiotherapy or chemoradiotherapy Head and neck tumors with in situ or cervical lymph node recurrence confirmed by pathological biopsy and imaging examination ECOG PS：0/1 Laboratory examination confirmed good organ function, which should be carried out within 10 days before the first treatment. Exclusion Criteria: After evaluation, it does not meet the indications of re-radiotherapy Unable to take oral medication Pregnancy or lactation Known allergy to penicillamine Patients who are judged by the researcher as unsuitable to participate in this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Penicillamine group<br>Participants in this group are treated with Penicillamine (250mg each time, 4 times per day) during reradiation. | Drug: Penicillamine<br>* Participants in this group are treated with Penicillamine (250mg each time, 4 times per day) during reradiation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | OS was defined as the time from the date of inclusion until death from any cause. | 2 years | 
| local-relapse free survival (LRFS) | LRFS was defined as the time from the date of inclusion until tumor relapse. | 2 years | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radiotherapy, radiosensitizer, penicillamine, copper