Evaluation of Avelumab Maintenance Immunotherapy Post-First-Line Platinum-Based Chemotherapy in Locally Advanced or Metastatic Squamous Cell Penile Carcinoma

Trial ID: 2024-514997-27-00
Protocol: P/2017/337
Sponsor: Centre Hospitalier Regional Universitaire

Trial statistics

science

test molecule

location_city

research sites

public

country

medical_information

disease

person_search

investigators

Diseases & Conditions

Penile squamous cell carcinoma

Objectives

The primary objective of this study is to evaluate the benefit of maintenance treatment with **avelumab** in patients with unresectable, locally advanced, or metastatic squamous cell penile carcinoma (SPC) whose disease has not progressed following first-line chemotherapy including cisplatin. This is measured by disease-free survival (DFS), which is clinically relevant as it provides insight into the efficacy of avelumab in prolonging the period during which the disease does not worsen.

Secondary objectives include:

Assessing the benefit of avelumab maintenance treatment measured by DFS according to iRECIST and overall survival (OS) in patients whose disease has not progressed after first-line polychemotherapy containing a platinum salt.
Evaluating the percentage of patients still alive at 12 months.
Assessing the duration of treatment with avelumab.
Evaluating DFS and OS of avelumab in patients with PD-L1 positive tumors and in all patients.
Assessing the overall safety profile of avelumab.
Evaluating the effect of avelumab on patients' health-related quality of life.
Assessing the time until subsequent first and second systemic therapy.
Evaluating the duration of administration of the first subsequent systemic therapy.
Estimating the time to deterioration of quality of life.

Participants

The clinical trial involves a study population consisting exclusively of **men** aged 18 years and older, diagnosed with unresectable locally advanced or metastatic **squamous cell penile carcinoma**. The trial does not include female participants, and the population is not considered vulnerable. Participants were selected based on specific criteria, including having completed a minimum of three and a maximum of six cycles of first-line polychemotherapy with a platinum salt, such as cisplatin or carboplatin, without disease progression as per RECIST v1.1 criteria. The trial requires participants to have an estimated life expectancy of at least three months and an ECOG performance status of 0 to 1. Adequate bone marrow, renal, and liver functions are also necessary for inclusion. The sponsor has not provided information regarding the total number of participants in the study.

Plans and Procedures

The clinical trial is designed to evaluate the **activity** and tolerability of maintenance **avelumab** immunotherapy in patients with locally advanced or metastatic squamous cell penile carcinoma (SPC) who have not shown disease progression following first-line polychemotherapy including a platinum salt. This is a Phase 4, randomized, double-blind, controlled trial with an estimated duration from October 2019 to October 2026. The primary objective is to assess disease-free survival (DFS) in this patient population. Secondary endpoints include overall survival (OS), the proportion of patients alive at 12 months, and the overall safety profile of avelumab.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, histological confirmation of SPC, and adequate organ function. Following the screening, eligible participants will be randomized to receive avelumab via infusion. Study visits will occur approximately every four weeks, coinciding with each treatment cycle, to monitor treatment response and adverse events. Quality of life will be assessed using the EORTC QLQ-C30 and EUROQOL EQ-5D questionnaires at baseline, during each cycle, upon study exit, and at disease progression if applicable.

The expected length of participant involvement is up to 24 months, depending on individual response and tolerability. Conditions that may lead to early termination from the study include disease progression, unacceptable toxicity, withdrawal of consent, or any other reason deemed appropriate by the investigator. The end-of-study visit will occur after the final treatment cycle or upon early termination, during which final assessments will be conducted to evaluate the primary and secondary endpoints.

Treatment

The clinical trial involves the use of **avelumab**, a recombinant human monoclonal IgG1 antibody targeting programmed death ligand-1 (PD-L1). Avelumab is administered in the form of an infusion, with a pharmaceutical form designated as PHF00230MIG. The dosage is calculated based on the patient's body weight, with a maximum daily dose of 10 mg/kg. The treatment is administered at a frequency determined by the study protocol, with a maximum treatment period of 24 months. The administration of avelumab is intended for patients with locally advanced or metastatic squamous cell penile carcinoma (SPC) who have not shown disease progression following first-line chemotherapy that includes cisplatin.

In this study, avelumab is the experimental medication, and there are no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments mentioned. The trial aims to evaluate the benefit of maintenance treatment with avelumab by measuring disease-free survival (DFS) in the specified patient population. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment regimen.

Efficacy

The efficacy of the clinical trial will be assessed primarily through the measurement of **disease-free survival (DFS)**. This parameter is defined as the time period between the initiation of avelumab treatment and the first occurrence of disease progression, as determined by RECIST v1.1 criteria, or death from any cause. Patients who are lost to follow-up or remain alive without disease progression will be censored at the date of last contact.

Secondary endpoints include overall survival (OS), which is the time from the start of treatment to death from any cause, and the proportion of patients alive at 12 months. Additionally, the duration of treatment with avelumab will be recorded, defined as the time from starting to permanently stopping the treatment. The trial will also assess DFS and OS in patients with PD-L1 positive tumors, using the DAKO/AGILENT clone IHC 22C3 for analysis.

Quality of life (QoL) will be evaluated using the EORTC QLQ-C30 and EUROQOL EQ-5D questionnaires at baseline, during each treatment cycle, upon study exit, and at disease progression if applicable. The trial will also measure survival without deterioration in quality of life, defined as the time from inclusion to the first clinically significant decline in QoL score without subsequent improvement or death.

The overall safety profile of avelumab will be described based on toxicity assessments following the CTCAE criteria, version 4.03. Additional analyses will include the time to first and second subsequent systemic therapies and the duration of administration of these therapies. These efficacy parameters will be collected and analyzed at specified intervals throughout the trial to ensure comprehensive evaluation of avelumab's impact on patients with locally advanced or metastatic squamous cell penile carcinoma.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Men, 18 years old and older
Histologically confirmed unresectable locally advanced or metastatic squamous cell penile carcinoma
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.
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)
Estimated life expectancy of at least 3 months
ECOG (Eastern Cooperative Group) performance status of 0 to 1
Adequate bone marrow function: a – absolute neutrophil (NP) count ≥ 1500/mm3 or ≥ 1.5x109/L b – platelets ≥ 100 000/mm3 or ≥ 100.109/L c – haemoglobin ≥ 9 g/dL (the patient may have been transfused)
Adequate renal function defined by a creatinine clearance of ≥ 30 m/min (according to the MDRD equation)
Adequate liver function: a – 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 b - AST (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤ 2.5 times ULN; the accepted limit in patients with liver metastases is ≤ 5 times ULN

cancel

Exclusion Criteria

Patients who have never received chemotherapy with a platinum salt (cisplatin or carboplatin)
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
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.
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.
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.
Patients with a past history of known central nervous system metastases, meningeal carcinomatosis or spinal compression
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.
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).
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
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.
Patients with uncontrolled adrenal failure.
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.
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).
Active infection requiring systemic treatment
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).
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)
Current treatment with an immunosuppressant medicinal product or treatment within 7 days prior to inclusion, EXCEPT: a – Intra-nasal, inhaled or local steroids or local steroid injections (such as intra-articular injections) b - Systemic corticosteroids at physiological doses of ≤ 10 mg/day of prednisone or equivalent c - Steroids as premedication for hypersensitivity reactions (such as CT scan premedication).
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
Previous organ transplant including stem cell allotransplantation.
Any screening test for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating active infection.
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).
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
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.
People who are vulnerable under the law (minors, adults under legal protection, people deprived of their freedom)