Avelumab as single agent in metastatic or locally advanced urothelial cancer in patients unfit for cisplatin. The ARIES Study
- Conditions
- metastatic or locally advanced urothelial cancerMedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-000670-29-IT
- Lead Sponsor
- CONSORZIO ONCOTECH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 67
•Informed consent obtained before any study-specific procedures. Patients must be able to understand and be willing to sign a written informed consent.
• Male or female patient =18 years of age.
• Histological or cytological documentation of urothelial cancer.
• Measurable or non-measurable disease according to Response Evaluation Criteria in Solid Tumors criteria, version 1.1.
•Positive (=5%) expression of PD-L1 on tumor cells evaluate by immunohistochemistry.
• Eastern Cooperative Oncology Group performance status of =2.
• Life expectancy of at least 6 months.
• Women of childbearing potential and men must agree to use adequate contraception since signing of the informed consent form until at least 3 months after the last study drug administration. The investigator or a designated associate is requested to advise the subject how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommend method (or combination of methods) as per standard of care.
• Adequate bone-marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days of starting to study treatment:
– Total bilirubin =1·5 × the upper limit of normal (ULN);
– Alanine aminotransferase and aspartate aminotransferase =2 × ULN (=5 × ULN for patients with liver involvement of their cancer);
– International normalized ratio (INR) and partial thromboplastin time (PTT) =1·5 × ULN. Subjects who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate if no prior evidence of an underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care;
– Platelet count =100 000/mm3, hemoglobin >9 g/dl, absolute neutrophil count >1,500/mm3;
– Alkaline phosphatase limit =2·5 × ULN (=5 × ULN for patients with liver involvement of their cancer).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 47
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
Prior treatment with avelumab.
• Previous treatment for metastatic or locally advanced disease.
• Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years before enrollment EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta [non-invasive tumor], Tis [carcinoma in situ], and T1 [tumor invades lamina propria]).
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication
• Pregnancy or breast-feeding. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment.
• Congestive heart failure of New York Heart Association class 3 or worse.
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of study drug.
• Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted).
• Uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg despite optimal medical management).
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), pulmonary embolism within the 4 months before start of study medication.
• Ongoing infection higher than National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 grade 2.
• Known history of human immunodeficiency (HIV) virus infection.
• Known history of chronic hepatitis B or C.
• Seizure disorder requiring medication.
• Symptomatic metastatic brain or meningeal tumors unless the patient is >2 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry. Also, the patient must not be undergoing acute steroid therapy or tapering (chronic steroid therapy is acceptable provided that the dose is stable for 1 month before and after screening radiographic studies).
• History of organ allograft.
• Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event of CTCAE grade 3 or higher within 4 weeks of start of study medication.
• Non-healing wound, ulcer, or bone fracture.
• Renal failure requiring hemodialysis or peritoneal dialysis.
• Dehydration of NCI-CTCAE version 5.0 grade 1 or higher.
• Substance abuse or medical, psychological, or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results.
• Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation.
• Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his or her compliance in the study.
• Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
• Unresolved toxicity higher than NCI-CTCAE version 5.0 grade 1 attributed to any prior therapy/procedure, excluding alopecia and cisplatin-induced neurotoxicity of grade 2 or less.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the activity of avelumab in patients with metastatic or locally advanced PD-L1 positive urothelial cancer not eligible for cisplatin-based chemotherapy.;Secondary Objective: -To evaluate the safety and avelumab in patients with metastatic or locally advanced urothelial cancer not eligible for cisplatin-based chemotherapy.<br>-To evaluate the quality of life assessed by EuroQoL EQ-5D and EORTC QLQ-C30.<br>-To evaluate the efficacy of avelumab in patients with recurrent/progressive metastatic urothelial cancer with different expression of PD-L1. <br>;Primary end point(s): This study aims to evaluate the anti-tumor efficacy of avelumab in patients with metastatic or locally advanced PD-L1 positive urothelial cancer not eligible for cisplatin-based chemotherapy. <br>Overall Survival (OS) is the best endpoint to demonstrate the efficacy of antineoplastic immunotherapy.<br>;Timepoint(s) of evaluation of this end point: 6 months after enrollment of the last patient
- Secondary Outcome Measures
Name Time Method