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Head and Neck Neoplasms

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Copper

Penicillamine

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Copper Supplement

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

Jian Guan, M.D

Jian Guan, M.D.

Jian Guan, MD

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.

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.

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

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

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.

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.

OS was defined as the time from the date of inclusion until death from any cause.

LRFS was defined as the time from the date of inclusion until tumor relapse.

treatment-related adverse events will be assessed by CTCAE v5.0

Nanfang Hospital, Southern Medical University

Nervous System Diseases

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Glioblastoma

Central Nervous System Neoplasms

Nervous System Neoplasms

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Neuroectodermal Tumors, Primitive

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Neuroepithelioma

penicillamine

radiation therapy

Steven Brem, MD

RATIONALE: Penicillamine may stop the growth of glioblastomas by stopping blood flow to the tumor. A diet low in copper may interfere with the growth of brain tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining these therapies may be effective in treating glioblastoma.

PURPOSE: Phase II trial to study the effectiveness of penicillamine, a low copper diet, and radiation therapy in treating patients who have newly diagnosed glioblastoma.

OBJECTIVES: I. Determine the effect of penicillamine and copper reduction on survival and time to progression in adults with newly diagnosed glioblastoma. II. Determine the effect of penicillamine on the reduction of serum copper in these patients. III. Determine whether penicillamine reduces the tumor volume, vascularity, invasion, and edema in these patients.

OUTLINE: Patients receive oral penicillamine on the following schedule: Week 1: once daily Week 2: two times daily Week 3: three times daily Week 4: four times daily Week 5 to end of study: increased dose four times daily. Patients also receive oral pyridoxine daily and maintain a low copper diet (no greater than 0.5 mg/day). This regimen is continued for up to 2 years in the absence of disease progression or unacceptable toxicity. Radiotherapy is administered over 6 weeks, beginning on day 1 of penicillamine therapy. Patients are followed every month (with MRI every 2 months) until death.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Penicillamine, Low Copper Diet, and Radiation Therapy in Treating Patients With Glioblastoma

Phase II Study of Penicillamine and Reduction of Copper for Angiosuppressive Therapy of Adults With Newly Diagnosed Glioblastoma

National Cancer Institute (NCI)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Superiority of Penicillamine in Radiosensitization of Recurrent Head and Neck Cancer	NCT06103617	Head and Neck C... Recurrent Cance...	Penicillamine	18 Years - 75 Years	Nanfang Hospital, Southern Medical University
Safety and Superiority of Penicillamine in Radiosensitization of Recurrent Head and Neck Cancer	NCT06103617	Head and Neck C... Recurrent Cance...	Penicillamine	18 Years - 75 Years	Nanfang Hospital, Southern Medical University
Penicillamine, Low Copper Diet, and Radiation Therapy in Treating Patients With Glioblastoma	NCT00003751	Brain and Centr...	penicillamine radiation thera...	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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