Clinical trial NCT06103617: Safety and Superiority of Penicillamine in Radiosensitization of Recurrent Head and Neck Cancer
Official title: Safety and Superiority of Penicillamine in Radiosensitization of Recurrent Head and Neck Cancer: a Single-center, Single-arm, Phase II Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Head and Neck Cancer
Recurrent Cancer
Keywords: radiotherapy
radiosensitizer
penicillamine
copper
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
First posted: 2023-10-27
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: 1 month
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 2 years
measure: local-relapse free survival (LRFS)
timeFrame: 2 years
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: During treatment and 12 weeks after penicillamine treatment
Other outcomes:
measure: the biomarkers correlated with ORR, LRFS and OS
timeFrame: 2 years
Locations:
city: Guangzhou
country: China
facility: Southern medical university
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital, Sourthern Medical University
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Jian Guan, M.D
role: PRINCIPAL_INVESTIGATOR
References: