Penile CancerPhase 2PERICLESNCT03686332
PEnile Cancer Radio- and Immunotherapy CLinical Exploration Study
A Phase 2 study testing Arm A: Atezolizumab and Radiotherapy and Arm B: Atezolizumab in people with Penile Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Penile Cancer
- What is being tested?
- Arm A: Atezolizumab and Radiotherapy and Arm B: Atezolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteNetherlands
- Study dates
- 25 Sep 2018to 15 Sep 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- 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.
Who cannot join
- 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.
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- 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
- Brain metastases or leptomeningeal disease. Inclusion of patients with brain metastases is allowed if patients have been adequately treated, are not symptomatic and show no signs of progression on brain imaging 28 days after completion of treatment (including surgery, radiotherapy or treatment with systemic corticosteroids).
- Subjects with uncontrolled seizures.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Netherlands Cancer Institute - Antoni van Leeuwenhoek
Amsterdam, North Holland, 1066 CX
About this study
Official title: PERICLES (PEnile Cancer Radio- and Immunotherapy CLinical Exploration Study)-a Phase 2 Study of Atezolizumab With or Without Radiotherapy in Penile Cancer
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.
Read the detailed description
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:
- Efficacy of atezolizumab in advanced penile cancer patients.
- 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.
- Conditions
- Penile Cancer
- Being tested
- Arm A: Atezolizumab and Radiotherapy, Arm B: Atezolizumab
- Keywords
- Radiotherapy, Immunotherapy, Atezolizumab
- Medical subject headings
- Penile Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arm A: Atezolizumab and RadiotherapyDrug
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 B: AtezolizumabDrug
patients will receive atezolizumab, 1200 mg, every 3 weeks, by IV infusion.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Arm A: Atezolizumab and Radiotherapy; Drug: Arm B: Atezolizumab |
| Arm B: Atezolizumab | Other | Atezolizumab, 1200 mg, every 3 weeks, by IV infusion. Receives: Drug: Arm A: Atezolizumab and Radiotherapy; Drug: Arm B: Atezolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival at 1 year.
Progression-free survival at 1 year.
Measured: 1 year
Secondary outcomes (1)
2-year overall survival rate of the complete study population.
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.
Measured: 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2018
- Study start25 Sep 2018
- Primary completion28 Sep 2022
- Study completion15 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Penile CancerStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Responsible party
- Sponsor
- Investigators
- Michiel MS van der Heijden, Dr., Principal investigator, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03686332
- Sponsor's protocol ID
- N18PER
- Other IDs
- 2018-000603-17, 2018
- Acronym
- PERICLES
- Status last verified
- Sep 2023
- First submitted
- 18 Sep 2018
- Last updated
- 21 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 37487169
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PERICLES (PEnile Cancer Radio- and Immunotherapy CLinical Exploration Study)-a Phase 2 Study of Atezolizumab With or Without Radiotherapy in Penile Cancer
- ClinicalTrials.gov ID
- NCT03686332
- Acronym / sponsor ID
- PERICLES / N18PER
- Conditions
- Penile Cancer
- Keywords
- Radiotherapy, Immunotherapy, Atezolizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- 25 Sep 2018 (actual)
- Primary completion
- 28 Sep 2022 (actual)
- Study completion
- 15 Sep 2023 (actual)
- First posted
- 26 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- Efficacy of atezolizumab in advanced penile cancer patients.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Arm A: Atezolizumab and Radiotherapy | Other | Drug: Arm A: Atezolizumab and Radiotherapy, Drug: Arm B: AtezolizumabPatients 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. |
| Arm B: Atezolizumab | Other | Drug: Arm A: Atezolizumab and Radiotherapy, Drug: Arm B: AtezolizumabAtezolizumab, 1200 mg, every 3 weeks, by IV infusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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)
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Arm A: Atezolizumab and Radiotherapypatients 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. | Drug | Arm A: Atezolizumab and Radiotherapy, Arm B: Atezolizumab |
| Arm B: Atezolizumabpatients will receive atezolizumab, 1200 mg, every 3 weeks, by IV infusion. | Drug | Arm A: Atezolizumab and Radiotherapy, Arm B: Atezolizumab |
Primary outcome
Progression-free survival at 1 year.
Time frame: 1 year
Progression-free survival at 1 year.
1 secondary outcome
2-year overall survival rate of the complete study population.
Time frame: 2 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2023.
- Derived from this study: PubMed 37487169de 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michiel MS van der Heijden, Dr. principal investigator
The Netherlands Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Arm A: Atezolizumab and Radiotherapy and Arm B: Atezolizumab in people with Penile Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival at 1 year. (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03686332, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2023.