PEnile Cancer Radio- and Immunotherapy CLinical Exploration Study

NCT03686332 | Completed Phase 2 DMC

• 2 other identifiers: N18PER2018-000603-17
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Penile Cancer

Keywords

Radiotherapy; Immunotherapy; Atezolizumab

Outcome Measures

Primary Outcomes (1)

• Progression-free survival at 1 year.

  Progression-free survival at 1 year.

  1 year

Secondary Outcomes (1)

• 2-year overall survival rate of the complete study population.

  2 year

Study Arms (2)

Arm A: Atezolizumab and Radiotherapy

OTHER

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.

Drug: Arm A: Atezolizumab and Radiotherapy; Drug: Arm B: Atezolizumab

Arm B: Atezolizumab

OTHER

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

Drug: Arm A: Atezolizumab and Radiotherapy; Drug: Arm B: Atezolizumab

Interventions

Arm A: Atezolizumab and Radiotherapy DRUG

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; Arm B: Atezolizumab

Arm B: Atezolizumab DRUG

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

Arm A: Atezolizumab and Radiotherapy; Arm B: Atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent, prior to performing any protocol-related procedures, including screening evaluations.
• Age \> 18 years at time of study entry.
• Advanced histologically documented, squamous cell carcinoma of the penis or distal urethra. Advanced disease is defined as:
• Distant metastases, OR
• LRAPC, defined as a large or inoperable primary tumor (T4), palpable nodes \>3cm in diameter or fixed nodes, suspicion of extra-nodal extension or pelvic node involvement (N2/N3)
• Arm A: Locoregional disease (with or without distant metastases), likely to derive benefit from locoregional radiotherapy and not previously treated with radiotherapy.
• Arm B: Benefit of locoregional radiotherapy unlikely OR previously treated with irradiation.
• World Health Organisation (WHO) performance status of 0 or 1.
• Life expectancy of \> 12 weeks.
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥ 5.6/mmol/L
• White blood cell count (WBC) ≥ 2 x 109/L
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L (\>100,000 per mm3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome, who will be allowed in consultation with a study physician.

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both Roche staff and/or staff at the study site) or previous enrolment in the present study.
• Participation in another clinical study with an investigational product during the last 4 weeks
• Any previous treatment with a PD-1 or PD-L1 inhibitor
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of study drug
• Low potential risk of 3-year cancer-specific death (estimated\<5%), including adequately treated non-melanoma skin cancer without evidence of disease, adequately treated carcinoma in situ without evidence of disease, or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (Gleason score ≤ 7 and PSA \< 10 ng/mL) undergoing active surveillance.
• Treatment with the last dose of any systemic anti-cancer therapy ≤ 21 days prior to the first dose of study drug. Local treatment of isolated lesions for palliative intent is acceptable (eg, local surgery or radiotherapy).
• Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at doses ≤10 mg/day of prednisone, or an equivalent corticosteroid.
• History of primary immunodeficiency, allogeneic organ transplant or autoimmune disease, including - but not limited to - myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone will not be excluded from this study. Patients with controlled diabetes mellitus type I on a stable dose of insulin regimen may be eligible for this study.
• Uncontrolled significant intercurrent illness, including - but not limited to - ongoing or active infection (including acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV)), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
• Known active tuberculosis
• Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
• Subjects with uncontrolled seizures.

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

Netherlands Cancer Institute - Antoni van Leeuwenhoek

Amsterdam, North Holland, 1066 CX, Netherlands

Location

Related Publications (1)

• de Vries HM, Rafael TS, Gil-Jimenez A, de Feijter JM, Bekers E, van der Laan E, Lopez-Yurda M, Hooijberg E, Broeks A, Peters D, Seignette IM, Pos FJ, Horenblas S, van Rhijn BWG, Jordanova ES, Brouwer OR, Schaake E, van der Heijden MS. Atezolizumab With or Without Radiotherapy for Advanced Squamous Cell Carcinoma of the Penis (The PERICLES Study): A Phase II Trial. J Clin Oncol. 2023 Nov 1;41(31):4872-4880. doi: 10.1200/JCO.22.02894. Epub 2023 Jul 24.

  PMID: 37487169 DERIVED

MeSH Terms

Conditions

Penile Neoplasms

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Penile Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Michiel MS van der Heijden, Dr.

  NKI-AvL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 18, 2018
• First Posted: September 26, 2018
• Study Start: September 25, 2018
• Primary Completion: September 28, 2022
• Study Completion: September 15, 2023
• Last Updated: September 21, 2023

Record last verified: 2023-09

Locations

NL (1)