Avelumab for Penile squamous cell carcinoma

Inclusion criteria

• {"criterion_text":"- Men, 18 years old and older"}
• {"criterion_text":"- Histologically confirmed unresectable locally advanced or metastatic squamous cell penile carcinoma"}
• {"criterion_text":"- Patients who have received a minimum of 3 and a maximum of 6 cycles of polychemotherapy including a platinum salt (cisplatin or carboplatin) administered as 1st line systemic treatment. In case of weekly or bi-monthly chemotherapy injection, the duration of one cycle can be of 3 weeks or 4 weeks depending on the drugs and doses prescribed. In the event of pretreatment with cisplatin: a cumulative minimum dose of 210 mg/m2 is required in order to be eligible. In the event of pretreatment with carboplatin: a minimum cumulative dose equivalent to 3 cycles of carboplatin AUC5 is required to be eligible."}
• {"criterion_text":"- Patients without disease-progression according to the RECIST v1.1 criteria (i.e. in complete or partial response or stable disease at inclusion) after 3 to 6 cycles of 1st line chemotherapy. Eligibility based on this criterion will be established locally by the investigator by examining pre and post-chemotherapy radiological assessments (CT/MRI)"}
• {"criterion_text":"- Estimated life expectancy of at least 3 months"}
• {"criterion_text":"- ECOG (Eastern Cooperative Group) performance status of 0 to 1"}
• {"criterion_text":"- Adequate bone marrow function: \ta – absolute neutrophil (NP) count ≥ 1500/mm3 or ≥ 1.5x109/L \tb – platelets ≥ 100 000/mm3 or ≥ 100.109/L \tc – haemoglobin ≥ 9 g/dL (the patient may have been transfused)"}
• {"criterion_text":"- Adequate renal function defined by a creatinine clearance of ≥ 30 m/min (according to the MDRD equation)"}
• {"criterion_text":"- Adequate liver function: \ta – total serum bilirubin ≤ 1.5 times ULN (upper limit of normal), except in cases of Gilbert’s disease when the authorised limit is ≤ 2 ULN \tb - AST (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤ 2.5 times ULN; the accepted limit in patients with liver metastases is ≤ 5 times ULN"}

Exclusion criteria

• {"criterion_text":"- Patients who have never received chemotherapy with a platinum salt (cisplatin or carboplatin)"}
• {"criterion_text":"- Active auto-immune disease which may deteriorate following administration of an immunostimulatory agent. Patients suffering from type I diabetes, vitiligo, psoriasis or hypo or hyperthyroidism not requiring immunosuppressant treatment are eligible."}
• {"criterion_text":"- Patients with uncontrolled adrenal failure."}
• {"criterion_text":"- Any of the following events in the 3 months prior to inclusion: myocardial infarction, severe/unstable angina, coronary/periphery artery bypass, symptomatic congestive heart failure, cerebrovascular accident, transient ischaemic attack."}
• {"criterion_text":"- Pulmonary embolism or deep vein thrombosis within 3 months prior to inclusion (unless if stable, asymptomatic and treated with a low molecular heparin for at least 10 days prior to starting the avelumab)."}
• {"criterion_text":"- Active infection requiring systemic treatment"}
• {"criterion_text":"- Known serious hypersensitivity reaction to monoclonal antibodies (grade ≤ 3), past history of anaphylaxis or uncontrolled asthma (i.e. three or more asthma symptom control factors according to the Global Initiative for Asthma, 2015)."}
• {"criterion_text":"- Known prior severe hypersensitivity to investigational product (avelumab) or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)"}
• {"criterion_text":"- Current treatment with an immunosuppressant medicinal product or treatment within 7 days prior to inclusion, EXCEPT: \ta – Intra-nasal, inhaled or local steroids or local steroid injections (such as intra-articular injections) \tb - Systemic corticosteroids at physiological doses of ≤ 10 mg/day of prednisone or equivalent \tc - Steroids as premedication for hypersensitivity reactions (such as CT scan premedication)."}
• {"criterion_text":"- Diagnosis of human immunodeficiency virus (HIV) infection or disease related to the acquired immunodeficiency syndrome (AIDS). In patients who are seropositive for HIV but have a disease deemed to be controlled on anti-viral therapy from the opinion of the patient’s HIV contact doctor: inclusion is still possible if the CD4 count is ≥ 300/mm3"}
• {"criterion_text":"- Previous organ transplant including stem cell allotransplantation."}
• {"criterion_text":"- Patients who have received more than one previous line of systemic treatment for penile cancer with the exception in case of a delay of more than 12 months between the end of a prior treatment and the start of the platinum based polychemotherapy"}
• {"criterion_text":"- Any screening test for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating active infection."}
• {"criterion_text":"- Vaccination within 4 weeks prior to the first administration of avelumab and throughout the period of the study, except with inactivated vaccines (such as, inactivated influenza vaccines)."}
• {"criterion_text":"- Men of child-bearing age who do not wish or cannot use 2 methods of highly effective contraception (oral contraceptives, contraceptive injections, intra-uterine devices, dual barrier method or contraceptive patches) as described in the protocol throughout the study and for at least 60 days after the last dose of avelumab"}
• {"criterion_text":"- Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study."}
• {"criterion_text":"- People who are vulnerable under the law (minors, adults under legal protection, people deprived of their freedom)"}
• {"criterion_text":"- Patients whose disease has progressed according to RECIST v1.1 criteria after 1st line chemotherapy for penile cancer. The cancer must not be in the progression phase at inclusion."}
• {"criterion_text":"- Past history of immunotherapy treatment with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or an anti- CTLA-4 antibody (including ipilimumab) or any other antibody or medicinal products specifically targeting anti-cancer immunotherapy."}
• {"criterion_text":"- Major surgery within 4 weeks or major radiotherapy within 2 weeks prior to starting avelumab. Previous palliative radiotherapy (≤ 10 fractions) for metastatic lesions is permitted provided that this has been completed at least 48 hours prior to starting avelumab."}
• {"criterion_text":"- Patients with a past history of known central nervous system metastases, meningeal carcinomatosis or spinal compression"}
• {"criterion_text":"- Persistent toxicity (excluding alopecia) due to previous treatment, NCI CTCAE v4.0 Grade> 1. Grade ≤2 sensory neuropathy, however is acceptable. If other residual grade ≤2 toxicities persist but do not carry a risk of decompensation on avelumab according to the investigator potential inclusion may be discussed with the sponsor."}
• {"criterion_text":"- Existence of a past history of cancer within 3 years prior to inclusion into the study (excluding cured localised cancer such as non-melanomatous skin cancers, superficial bladder cancers and localised prostate cancer with undetectable PSA)."}
• {"criterion_text":"- Participation in another interventional study with a systemic anti-cancer treatment within 4 weeks prior to inclusion. Inclusion in observational or interventional studies not involving a health product is permitted. Patients with telephone follow up of toxicities and simple laboratory monitoring or other questionnaires alone may be included"}

Primary endpoints

• {"endpoint_text":"- Disease-free progression (DFS): time period between the date of starting avelumab and the date of first progression (local, remote [measurement of disease according to RECIST v1.1 criteria], second cancer) or death regardless of cause. The patients lost to follow up and patients who are alive without disease progression will be censured at the date of last news.","definition_or_measurement_approach":"DFS defined as time from start of avelumab to first progression (local or remote measured according to RECIST v1.1 criteria) or second cancer or death; patients lost to follow-up or alive without progression are censored at date of last news."}

Secondary endpoints

• {"endpoint_text":"- Overall survival (OS) defined as the time period between the date of starting treatment and the date of death, regardless of cause. Patients lost to follow up and those who are alive will be censured at the date of last news.","definition_or_measurement_approach":"OS defined as time from start of treatment to death from any cause; patients lost to follow-up or alive are censored at date of last news."}
• {"endpoint_text":"- Proportion of patients who are alive at 12 months: number of patients alive at 12 months divided by the number of patients included initially; patients lost to follow up at 12 months will not be included in this analysis and those lost to follow up will be censured at the date of last news.","definition_or_measurement_approach":"Proportion alive at 12 months = patients alive at 12 months / number included; lost to follow-up at 12 months excluded from analysis; lost to follow-up censored at last news."}
• {"endpoint_text":"- Duration of treatment with avelumab defined as the time between starting avelumab and permanently stopping avelumab regardless of cause. Patients still on treatment with avelumab at the date the data are frozen will be censured","definition_or_measurement_approach":"Time from start of avelumab to permanent discontinuation; ongoing patients censored at data freeze."}
• {"endpoint_text":"- Assessment of DFS and OS of avelumab in patients with a PD-L1 positive tumour. The definition of DFS and OS is the same and the analyses will be performed with the various positivity thresholds for PD-L1. DAKO/AGILENT clone IHC 22C3 will be the clone chosen","definition_or_measurement_approach":"DFS and OS analyses stratified by PD-L1 positivity thresholds using DAKO/Agilent IHC 22C3 clone."}
• {"endpoint_text":"- The overall safety profile of avelumab will be described from the assessment of toxicity following the CTCAE (Common Terminology Criteria for Adverse Events) criteria, version 4.03.","definition_or_measurement_approach":"Safety assessed by CTCAE v4.03 toxicity grading."}
• {"endpoint_text":"- The times to the 1st and 2nd subsequent systemic therapy (TJPTSU; TJDTSU) are defined as the time period between the avelumab start date and the date of starting the 1st or 2nd anticancer treatment administered for SPC after failure of avelumab therapy. Patients who did not receive any subsequent treatment or who have died prior to receiving subsequent treatment will be censured.","definition_or_measurement_approach":"Time from avelumab start to start of 1st/2nd subsequent systemic anticancer therapy; patients without subsequent therapy or who died before subsequent therapy are censored."}
• {"endpoint_text":"- Duration of administration of the first/subsequent systemic treatment defined as the time interval between starting the first/subsequent systemic therapy and permanently stopping this therapy regardless of cause. Patients still on treatment with first/subsequent systemic therapy at the date the data are frozen will be censured.","definition_or_measurement_approach":"Time from start to permanent stop of first/subsequent systemic therapy; ongoing patients censored at data freeze."}
• {"endpoint_text":"- QoL will be assessed from the EORTC QLQ-C30 and EUROQOL EQ-5D questionnaires at baseline, D1 of each cycle (approximately 4 weeks), on leaving the study and on disease progression (if the study leaving date and date of progression differ by more than 4 weeks).","definition_or_measurement_approach":"Quality of life measured using EORTC QLQ-C30 and EQ-5D at specified timepoints (baseline, day 1 of each ~4-week cycle, study exit, and at progression if >4 weeks difference)."}
• {"endpoint_text":"- Survival without deterioration in quality of life (QFS) assessed from the QLQ-C30 questionnaire defined as the time interval between the date of inclusion and first minimum clinically significant difference (MCSD) in the score at inclusion without significant clinical improvement subsequently or death, regardless of cause.","definition_or_measurement_approach":"QFS defined as time from inclusion to first MCSD in QLQ-C30 score without subsequent significant improvement, or death."}

France

Earliest CTIS Part Ii Submission Date

31-10-2024

Latest Decision Or Authorization Date

03-12-2024

Processing Time Days

33

Number Of Sites

4

Number Of Participants

28

Primary sponsor

Full Name

Centre Hospitalier Regional Universitaire

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France