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

NCT03891238 | Completed Phase 2 DMC

• 1 other identifier: ARIES
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 21

Brief Summary

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

Conditions

Metastatic or Locally Advanced PD-L1 Positive Urothelial Cancer

Keywords

unfit for cisplatin; PD-L1; urotelian metastatic cancer

Outcome Measures

Primary Outcomes (1)

• Efficacy Endpoints

  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.

  2years

Secondary Outcomes (4)

• Median Progression-Free Survival (mPFS)

  18 months

• Objective response rate (ORR)

  18 months

• Safety Endpoints

  2 years

• Patient Reported Outcomes (PRO)

  2 years

Other Outcomes (1)

• Exploratory Objective(s)

  2 years

Study Arms (1)

Avelumab Arm

EXPERIMENTAL

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

Drug: Avelumab

Interventions

Avelumab DRUG

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

Avelumab Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able to understand and be willing to sign a written informed consent for the trial. Informed consent obtained before any study-specific procedures.
• Be Male or female patient ≥18 years of age on day of signing informed consent.
• Have histologicallly or cytologically-confirmed diagnosis of urothelial cancer of the renal pelvis, ureter, bladder, or urethra. Both transitional cell and mixed transitional/non-transitional cell histologies are allowed, but transitional cell carcinoma must be the predominant histology. Subjects with non-urothelial cancer of the urinary tract are not allowed.
• Have measurable or non-measurable disease according to Response Evaluation Criteria in Solid Tumors criteria (RECIST), version 1.1.
• Have immunohistochemical expression of PD-L1 ≥ 5% on tumor cells in archived tumor biopsies.
• Have a performance status of ≤2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale, as assessed within 10 days prior to treatment initiation.
• Have a life expectancy of at least 6 months.
• Female subject 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. Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after last avelumab treatment administration if the risk of conception exists. Adequate contraception is defined in the study as any medically recommend method (or combination of methods) as per standard of care.
• Respect the Cisplatin-unfit criteria, defined if at least one of these characteristics is present:
• \. ECOG-Performance status = 2;
• Creatinine Clearance \< 60 ml/min;
• Grade 2 or worse peripheral neuropathy or hearing loss;
• Previous treatment with cisplatin for adjuvant intent in six months before the progression of disease.
• Demonstrate adequate bone-marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days of starting to study treatment:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused);

You may not qualify if:

• Has disease that is suitable for local therapy administered with curative intent.
• Has received prior treatment with avelumab.
• Has received prior therapy with an anti-PD-1 or anti-PD-L1 agent, or with an agent directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137).
• Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v 5.0 Grade ≥ 3).
• Has received previous treatment for metastatic or locally advanced urothelial cancer.
• Has a known previous or concurrent malignancy that is progressing or requires active treatment and is distinct in primary site or histology from urothelial cancer within 5 years before randomization.
• Exceptions cervical cancer in situ or basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy. A history of prostate cancer that was identified incidentally following cystoprostatectomy for bladder cancer is acceptable, provided that the following criteria are met:
• Stage T2N0M0 or lower;
• Gleason score ≤ 6,
• PSA undetectable.
• Has major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication
• Has active cardiac disease, defined as:
• Myocardial infarction or unstable angina pectoris within 6 months of the first date of study therapy.
• History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation.
• New York Heart Association (NYHA) Class III or greater congestive heart failure, or left ventricular ejection fraction of \< 40%.

Sponsors & Collaborators

• Consorzio Oncotech: lead

Study Sites (21)

Istituto Tumori "Giovanni Paolo II" IRCCS Ospedale Oncologico di Bari

Bari, 70124, Italy

Location

ASST Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Ospedale Santa Croce - A.O. Ospedali Riuniti Marche Nord

Fano, 60132, Italy

Location

IRCCS Ospedale Policlinico San Martino

Genova, 16132, Italy

Location

Ospedale di Macerata - ASUR - Area Vasta N°3

Macerata, 62100, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

INT- IRCCS - Foundation G. Pascale

Napoli, 80131, Italy

Location

AOU San Luigi Gonzaga

Orbassano, 10043, Italy

Location

Azienda Ospedaliera Universitaria di Parma

Parma, 43126, Italy

Location

Fondazione Salvatore Maugeri

Pavia, 27100, Italy

Location

A.O. Ospedali Riuniti Marche Nord

Pesaro, 61121, Italy

Location

Azienda Ospedalieo-Universitaria Pisana

Pisa, 56126, Italy

Location

Arcispedale Santa Maria Nuova Di Reggio Emilia

Reggio Emilia, 42123, Italy

Location

Policlinico Universitario Campus Bio Medico

Roma, 00128, Italy

Location

Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, 00168, Italy

Location

Ospedale "S. Vincenzo" di Taormina

Taormina, 98039, Italy

Location

Azienda Ospedaliera Santa Maria

Terni, 05100, Italy

Location

Presidio Ospedaliero "Santa Maria Della Misericordia" Di Udine Sede Di Udine

Udine, 33010, Italy

Location

Az.Osp.Universitaria Integrata Verona- Borgo Trento

Verona, 37126, Italy

Location

ULSS 8 Berica- Ospedale San Bortolo di Vicenza

Vicenza, 36100, Italy

Location

Related Publications (4)

• Agata Y, Kawasaki A, Nishimura H, Ishida Y, Tsubata T, Yagita H, Honjo T. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int Immunol. 1996 May;8(5):765-72. doi: 10.1093/intimm/8.5.765.

  PMID: 8671665 BACKGROUND

• Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992 Nov;11(11):3887-95. doi: 10.1002/j.1460-2075.1992.tb05481.x.

  PMID: 1396582 BACKGROUND

• Blank C, Brown I, Peterson AC, Spiotto M, Iwai Y, Honjo T, Gajewski TF. PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res. 2004 Feb 1;64(3):1140-5. doi: 10.1158/0008-5472.can-03-3259.

  PMID: 14871849 BACKGROUND

• Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002 Aug;8(8):793-800. doi: 10.1038/nm730. Epub 2002 Jun 24.

  PMID: 12091876 BACKGROUND

Related Links

• ARIES trial

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

avelumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: March 25, 2019
• First Posted: March 26, 2019
• Study Start: February 6, 2019
• Primary Completion: September 15, 2021
• Study Completion: September 15, 2021
• Last Updated: February 1, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (21)