Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Penile Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Penile Diseases

Male Urogenital Diseases

Penile Cancer

Antineoplastic Agents

All Drugs and Chemicals

Atezolizumab

Immunomodulating Agents

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Immunologic Factors

Patients in this group will concurrently be treated with locoregional radiotherapy and atezolizumab.

Drug: Arm A: Atezolizumab and Radiotherapy

Atezolizumab, 1200 mg, every 3 weeks, by IV infusion and receive 33 fractions of 1.5 or 1.8 Gy irradiation.

Atezolizumab, 1200 mg, every 3 weeks, by IV infusion.

patients will receive atezolizumab, 1200 mg, every 3 weeks, by IV infusion. Patients in group A will additionally receive 33 fractions of 1.5 (locoregional affected lymph nodes) and 1.8 Gy (tumor+margin) irradiation, concurrently with atezolizumab treatment.

Arm A: Atezolizumab and Radiotherapy

patients will receive atezolizumab, 1200 mg, every 3 weeks, by IV infusion.

Arm B: Atezolizumab

Michiel MS van der Heijden, Dr.

Patients with advanced penile cancer have a poor prognosis (21% 2-year overall survival from moment of diagnosis) and high morbidity due to progressive locoregional disease.

Translational studies show high rates of infiltrating immune cells and PD-L1 positivity, suggesting that immunotherapy may be beneficial in this disease. Atezolizumab, targeting PD-L1, is active in several cancer types and is generally well-tolerated. This study will investigate whether atezolizumab can be combined with radiotherapy to control locoregional lymph node disease. Furthermore, the activity of atezolizumab in advanced penile cancer patients will be investigated.

Rationale Patients with advanced penile cancer have a poor prognosis (21% 2-year overall survival from moment of diagnosis) and high morbidity due to progressive locoregional disease.

Translational studies show high rates of infiltrating immune cells and PD-L1 positivity, suggesting that immunotherapy may be beneficial in this disease. Atezolizumab, targeting PD-L1, is active in several cancer types and is generally well-tolerated. This study will investigate whether atezolizumab can be combined with radiotherapy to control locoregional lymph node disease. Furthermore, the activity of atezolizumab in advanced penile cancer patients will be investigated.

Objectives:

1. Efficacy of atezolizumab in advanced penile cancer patients.
2. Feasibility of a protracted schedule of radiotherapy on locoregional disease in combination with immunotherapy for advanced penile cancer

Study design:

Single-center, nonrandomized, Phase 2 study with 2 treatment arms.

Study population:

Men, ≥18 years of age, with advanced inoperable penile cancer, N=32.

Intervention:

All patients will receive atezolizumab, 1200 mg, every 3 weeks, by IV infusion. Patients in group A will additionally receive 33 fractions of 1.5 (locoregional affected lymph nodes) and 1.8 Gy (tumor+margin) irradiation, concurrently with atezolizumab treatment.

Primary endpoint:

Progression-free survival at 1 year.

Main secondary endpoint:

2-year overall survival rate of the complete study population. Percentage of patients who complete the full course of radiotherapy in the radiotherapy/atezolizumab arm.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients will be treated every 3 weeks with atezolizumab for one year or until loss of clinical benefit. Atezolizumab is generally well tolerated although immune-related toxicity does occur.

Toxicity of combining atezolizumab with a long course of radiotherapy is unknown and may result in increased toxicity. It is unknown whether atezolizumab will induce responses in patients with advanced penile cancer.

All patients included will have unresectable advanced penile cancer. Patients will be discussed in multi-disciplinary rounds to establish this criterion. Two treatment groups will be distinguished.

Arm A: Patients with locoregional lymph node disease who have not received extensive inguinal or pelvic irradiation on the involved area before. Patients in this group will concurrently be treated with locoregional radiotherapy and atezolizumab.

Arm B: Patients who are not expected to derive benefit from radiotherapeutic treatment. This group will mainly consist of patients with distant metastases or previously treated locoregional disease and will only be treated with atezolizumab.

PEnile Cancer Radio- and Immunotherapy CLinical Exploration Study

PERICLES (PEnile Cancer Radio- and Immunotherapy CLinical Exploration Study)-a Phase 2 Study of Atezolizumab With or Without Radiotherapy in Penile Cancer

The key secondary outcome measure will be 2-year overall survival rate in the full study cohort (Arm A and B combined).

radiotherapy/atezolizumab arm.

Spots Global Cancer Trial Database for arm b: atezolizumab