Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Antineoplastic Agents

All Drugs and Chemicals

Avelumab

Cisplatin

Antineoplastic Agents, Immunological

Patients will receive avelumab at standard dosage of 10 mg/kg as a 1-hour intravenous infusion once every 2 weeks (Q2W).

This is a single arm, open label, phase II study to evaluate the activity of avelumab (MSB0010718C) in patients with metastatic or locally advanced urothelial cancer considered unfit to cisplatin-based chemotherapy, to be conducted in conformance with Good Clinical Practices.

Cisplatin-unfit patients will be defined if at least one of these characteristics is present:

1. ECOG-Performance status = 2;
2. Creatinine Clearance \< 60 ml/min;
3. Grade 2 or worse peripheral neuropathy or hearing loss;
4. Previous treatment with cisplatin for adjuvant intent in six months before the progression of disease.

Each subject will participate in the trial from the time the subject signs the Informed Consent Form (ICF) through the final contact. After a screening phase of 28 days, each subject will receive the treatment. Treatment on trial will continue until disease progression is confirmed by the investigator/site radiologist, unacceptable adverse event(s), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, subject withdrawals consent, pregnancy of the subject, noncompliance with trial treatment or procedures requirements, or administrative reasons.

The study treatment may be continued after radiological progression of disease at physician discretion and if improvement of symptoms or not new symptoms were reported by the patient despite the radiological progression of disease.

Subjects who attain a complete response may consider stopping trial treatment if they meet criteria for holding therapy.

After the end of treatment given the potential risk for delayed immune-related toxicities, safety follow-up must be performed up to 90 days after the last dose of avelumab administration.

The extended safety follow-up beyond 30 days after last study drug administration may be performed either via a site visit or via a telephone call with subsequent site visit requested in case any concerns noted during the telephone call.

Subjects who discontinue for reasons other than disease progression will have post-treatment follow-up every 12 weeks for disease status until disease progression is confirmed by the investigator/site radiologist, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. All subjects will be followed by telephone for overall survival every 12 weeks until death, withdrawal of consent, or the end of the trial.

To assess the activity of avelumab in patients with metastatic or locally advanced PD-L1 positive urothelial cancer not eligible for cisplatin-based chemotherapy.

Avelumab as Single Agent in Metastatic or Locally Advanced Urothelial Cancer in Patients Unfit for Cisplatin. The ARIES Study

Avelumab as Single Agent in Metastatic or Locally Advanced Urothelial Cancer in Patients Unfit for Cisplatin

Exploratory analysis will evaluate the predictive/prognostic role of the immunohistochemical expression of PD1/PD-L1 in tumor tissue samples of subjects with recurrent/progressive metastatic urothelial cancer not eligible for cisplatin-based chemotherapy and treated with avelumab.

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.

OS is defined as the time from study entry to the date of death (whatever the cause). The survival time of living patients will be censored at last date on which the patient is known to be alive or lost to follow-up. Subject status will be followed every 2 weeks while on treatment and then every 3 months thereafter.

• 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.

• 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.

The first on study radiographic imaging assessment will be performed at 8 weeks (± 7 days) after first dose of study treatment and then every 12 weeks (± 7 days) thereafter or more frequently if clinically indicated.

PR are those with greater than or equal to 30 percent decrease in the sum of the products of diameters (SOPD) of index lesions compared to the baseline SOPD, with no evidence of progressive disease (PD).

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.

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 (extreme problem) to 3 (no problem). The eEQ-5D also includes a graded (0 to 100) vertical visual analog scale on which the patient rates his or her general state of health at the time of the assessment. The eEQ-5D is to be completed at various time points as specified in the study Flow Chart, beginning with Cycle 1 until 30 days post-treatment discontinuation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Avelumab as Single Agent in Metastatic or Locally Advanced Urothelial Cancer in Patients Unfit for Cisplatin. The ARIES Study	NCT03891238	Metastatic or L...	Avelumab	18 Years -	Consorzio Oncotech
Avelumab as Single Agent in Metastatic or Locally Advanced Urothelial Cancer in Patients Unfit for Cisplatin. The ARIES Study	NCT03891238	Metastatic or L...	Avelumab	18 Years -	Consorzio Oncotech

Spots Global Cancer Trial Database for urotelian metastatic cancer