metastatic or locally advanced urothelial cancer MedDRA version: 20.0 Level: LLT Classification code 10064467 Term: Urothelial carcinoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Avelumab
Pharmaceutical Form: Concentrate for solution for infusion
Current Sponsor code: MSB0010718C
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentr
Sponsors
CONSORZIO ONCOTECH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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
Exclusion criteria
Exclusion criteria: 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. -To evaluate the quality of life assessed by EuroQoL EQ-5D and EORTC QLQ-C30. -To evaluate the efficacy of avelumab in patients with recurrent/progressive metastatic urothelial cancer with different expression of PD-L1. ;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. Overall Survival (OS) is the best endpoint to demonstrate the efficacy of antineoplastic immunotherapy. ;Timepoint(s) of evaluation of this end point: 6 months after enrollment of the last patient | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Median Progression-Free Survival (mPFS) mPFS: calculated from the date of study entry (first administration of avelumab) to date of documented radiographic progression or death according to RECIST Version 1.1 criteria. The primary analyses of PFS will be based on investigator’s assessments using RECIST 1.1 criteria.; Objective response rate (ORR) ORR: defined as complete response (CR) or partial response (PR) according to RECIST Version 1.1 criteria as determined by investigator’s assessments, obtained from start of study drug until documented radiographic disease progression.; Safety Endpoints The primary safety objective of this trial is to characterize the safety and tolerability of avelumab in subjects with recurrent/progressive metastatic urothelial cancer not eligible for cisplatin-based chemotherapy. The primary safety analysis will be based on subjects who experienced toxicities as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 criteria. Safety will be assessed by quantifying the toxicities and grades experienced by subjects who have received avelumab, including serious adverse events (SAEs) and events of clinical interest (ECIs). Safety will be assessed by reported adverse events (AEs) according to NCI CTCAE version 5.0.; Patient Reported Outcomes (PRO) PRO are not pure efficacy or safety endpoints because they are affected by both disease progression and treatment tolerability. The study aims to evaluate the quality of life assessed by EuroQoL EQ-5D. The eEuroQol-5D (eEQ-5D) is a standardized instrument for use as a measure of health outcome. The eEQ-5D will provide data for use in economic models and analyses including developing health utilities or QALYs. The five health state dimensions in this instrument include the following: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a three-point scale from 1 (extr | — |
Countries
Italy
Contacts
Public ContactDipartimento ad Attività Integrata
AZ.OSP.UNIVERSITARIA INTEGRATA VERONA- BORGO TRENTO
Outcome results
None listed