PERICLES (PEnile cancer Radio- and Immunotherapy CLinical Exploration Study) - a Phase 2 study of atezolizumab with or without radiotherapy in penile cancer

Phase 2

Completed

Conditions: Penile cancer
10038597
10013355

Registration Number: NL-OMON52808

Lead Sponsor: Antoni van Leeuwenhoek Ziekenhuis

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 32

Inclusion Criteria

- 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. , Adequate normal organ and marrow
function as defined below: , -Haemoglobin >= 5.6/mmol/L, -White blood cell
count (WBC) >= 2 x 109/L (> 1500 per mm3), -Absolute neutrophil count (ANC) >=
1.5 x 109/L (> 1500 per mm3), -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., -AST/ALT <= 2.5 x institutional
ULN unless liver metastases are present, in which case it must be <= 5x ULN.,
-Serum creatinine clearance >30 mL/min by calculation with the
Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine
collection measurement.

Exclusion Criteria

1. Involvement in the planning and/or conduct of the study (applies to both
Roche staff and/or staff at the study site). Previous enrolment in the present
study., 2. Participation in another clinical study with an investigational
product during the last 4 weeks, 3. Any previous treatment with a PD1 or PD-L1
inhibitor, 4. 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., 5. 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). , 6. 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 systemic doses
below <= 10 mg/day of prednisone, or an equivalent corticosteroid., 7. 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 1 on a stable dose of insulin regimen
may be eligible for this study. , 8. Uncontrolled 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, 9. Known active tuberculosis, 10. Any condition that, in the opinion
of the investigator, would interfere with evaluation of study treatment or
interpretation of patient safety or study results, 11. Brain metastases or
leptomeningeal disease. Inclusion of patients with brain metastases is allowed
if patients have been adequately treated and no signs of progression on brain
imaging >=*28 days after completion of treatment (including surgery,
radiotherapy or treatment with systemic corticosteroids). , 12. Subjects with
uncontrolled seizures.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Progression-free survival (PFS) at 1 year after initiation of treatment. A PFS<br /><br>event is defined as RECIST 1.1 progressive disease (appearance of new lesions<br /><br>or progression of existing target/nontarget lesions) or death from any cause.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Overall Survival (OS) rate at 2 years in the full study population<br /><br>- Feasibility of combining immunotherapy with radiotherapy as measured by<br /><br>number of patients who complete the combined modality treatment (Arm A).<br /><br>Completion is defined as having received at least 90% of planned radiation<br /><br>doses.<br /><br>- Locoregional Recurrence-free survival in patients treated with the<br /><br>combination of radiotherapy and atezolizumab (arm A)<br /><br>- Response rate for patients with measurable disease<br /><br>- Median PFS (as measured by RECIST 1.1) and OS for the full study cohort (Arm<br /><br>A+B)<br /><br>- 2-year PFS (as measured by RECIST 1.1) and OS for PD-L1-positive patients in<br /><br>the full study cohort (Arm A+B)<br /><br>- Toxicity by CTCAE-NCI V4 in the combined modality arm</p><br>