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.
Condition or disease | Intervention/treatment | Phase |
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Penile Cancer | Drug: Arm A: Atezolizumab and Radiotherapy Drug: Arm B: Atezolizumab | Phase 2 |
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:
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 Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 32 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Intervention 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) |
Primary Purpose: | Treatment |
Official Title: | PERICLES (PEnile Cancer Radio- and Immunotherapy CLinical Exploration Study)-a Phase 2 Study of Atezolizumab With or Without Radiotherapy in Penile Cancer |
Actual Study Start Date : | September 25, 2018 |
Estimated Primary Completion Date : | December 30, 2021 |
Estimated Study Completion Date : | December 1, 2022 |
Arm | Intervention/treatment |
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Arm A: Atezolizumab and Radiotherapy
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
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.
Drug: Arm B: Atezolizumab patients will receive atezolizumab, 1200 mg, every 3 weeks, by IV infusion.
|
Arm B: Atezolizumab
Atezolizumab, 1200 mg, every 3 weeks, by IV infusion.
|
Drug: Arm A: Atezolizumab and Radiotherapy
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.
Drug: Arm B: Atezolizumab patients will receive atezolizumab, 1200 mg, every 3 weeks, by IV infusion.
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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.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Male |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Michiel MS van der Heijden, Dr. | +31 20 512 ext 9111 | ms.vd.heijden@nki.nl | |
Contact: Hielke HM de Vries, M.D. | +31 20 512 ext 9111 | hm.d.vries@nki.nl |
Netherlands | |
Netherlands Cancer Institute - Antoni van Leeuwenhoek | Recruiting |
Amsterdam, Noord- Holland, Netherlands, 1066 CX | |
Contact: Michiel MS Heijden van der,, MD +31 20 512 ext 9111 ms.vd.heijden@nki.nl | |
Contact: Hielke HM Vries, de +31 20512 ext 9111 hm.d.vries@nki.nl |
Principal Investigator: | Michiel MS van der Heijden, Dr. | NKI-AvL |
Tracking Information | |||||||||
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First Submitted Date ICMJE | September 18, 2018 | ||||||||
First Posted Date ICMJE | September 26, 2018 | ||||||||
Last Update Posted Date | March 25, 2021 | ||||||||
Actual Study Start Date ICMJE | September 25, 2018 | ||||||||
Estimated Primary Completion Date | December 30, 2021 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
Progression-free survival at 1 year. [ Time Frame: 1 year ] Progression-free survival at 1 year.
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
2-year overall survival rate of the complete study population. [ Time Frame: 2 year ] 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.
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | PEnile Cancer Radio- and Immunotherapy CLinical Exploration Study | ||||||||
Official Title ICMJE | PERICLES (PEnile Cancer Radio- and Immunotherapy CLinical Exploration Study)-a Phase 2 Study of Atezolizumab With or Without Radiotherapy in Penile Cancer | ||||||||
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. |
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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:
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. |
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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 2 | ||||||||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Intervention 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. Primary Purpose: Treatment |
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Condition ICMJE | Penile Cancer | ||||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
32 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | December 1, 2022 | ||||||||
Estimated Primary Completion Date | December 30, 2021 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | Netherlands | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT03686332 | ||||||||
Other Study ID Numbers ICMJE | N18PER 2018-000603-17 ( EudraCT Number ) |
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Has Data Monitoring Committee | Yes | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||||||
Responsible Party | The Netherlands Cancer Institute | ||||||||
Study Sponsor ICMJE | The Netherlands Cancer Institute | ||||||||
Collaborators ICMJE | Hoffmann-La Roche | ||||||||
Investigators ICMJE |
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PRS Account | The Netherlands Cancer Institute | ||||||||
Verification Date | March 2021 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |