Clinical trial NCT06534983: A Study to Evaluate the Efficacy and Safety of Autogene Cevumeran With Nivolumab Versus Nivolumab Alone in Participants With High-Risk Muscle-Invasive Urothelial Carcinoma (MIUC)
Official title: A Randomized Phase II, Double-Blind, Multicenter Study Evaluating the Efficacy and Safety of Autogene Cevumeran Plus Nivolumab Versus Nivolumab as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Urothelial Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Muscle Invasive Urothelial Carcinoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: BioNTech SE
First posted: 2024-08-02
Enrollment: 362
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of the study is to evaluate the efficacy of adjuvant treatment with autogene cevumeran plus nivolumab compared with nivolumab in participants with high risk MIUC.

In this study participants will be enrolled in a safety run-in phase to receive autogene cevumeran + nivolumab. This phase will be conducted to monitor and ensure the safety of study participants. After all participants in the safety run-in have been enrolled to receive autogene cevumeran + nivolumab, further participants will be randomization in either autogene cevumeran + nivolumab or the saline + nivolumab arm.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed muscle-invasive UC (also termed TCC) of the bladder or upper urinary tract
* TNM classification (UICC/AJCC 7th edition) at pathological examination of surgical resection specimen of (y)pT3-4 or (y)pN+ and M0
* Surgical resection of MIUC of the bladder or upper tract
* Participants who have not received prior neoadjuvant cisplatin chemotherapy (NAC) must be ineligible to receive adjuvant cisplatin therapy due to patient refusal, cisplatin ineligibility or investigator decision
* Tumor tissue must be provided for biomarker analysis
* Absence of residual disease and absence of metastasis, as confirmed by a negative baseline Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan of the pelvis, abdomen, and chest no more than 28 days prior to randomization.
* Full recovery from cystectomy or nephroureterectomy within 120 days following surgery
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Negative HIV test at screening
* No evidence of active hepatitis B, defined as having a negative hepatitis B surface antigen (HbsAg) test at screening
* Negative hepatitis C virus (HCV) antibody test at screening, or a positive HCV antibody test followed by a negative HCV RNA test at screening

Exclusion Criteria:

* Partial cystectomy in the setting of bladder cancer primary tumor or partial nephroureterectomy in the setting of renal pelvis primary tumor
* Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment
* Any prior neoadjuvant immunotherapy
* Adjuvant chemotherapy or radiation therapy for UC following surgical resection
* Malignancies other than UC within 5 years prior to randomization
* Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment

Primary outcomes:
measure: Investigator Assessed Disease Free Survival (INV-DFS)
timeFrame: Randomization until the first recurrence of disease or death from any cause, whichever occurs first (approximately 6 years )
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Randomization until the date of death from any cause (approximately 6 years)
measure: Investigator Assesed DFS in Programmed Death Ligand-1 (PD-L1) Expression ≥ 1% Population
timeFrame: Randomization until first occurrence of a documented disease recurrence or death from any cause, whichever occurs first (approximately 6 years)
measure: Investigator Assessed Distant Metastasis-Free Survival (DMFS)
timeFrame: Randomization to the date of diagnosis of distant (i.e., non-locoregional) metastases (approximately 6 years)
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to approximately 22 months
measure: Change From Baseline in Participant-reported Pain, Physical Function, Role Function and Quality of Life (QoL) as Assessed Using European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC QLQ-C30)
timeFrame: From Day 1 up to approximately 25 months
measure: Number of Participants With Symptomatic Treatment Toxicities as Assessed by National Cancer Institute Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE)
timeFrame: From Day 1 up to Cycle 21 (cycle length=28 days)
measure: Number of Participants Experiencing AE Burden due to Treatment as Assessed by EORTC Item Library 46 (IL46)
timeFrame: From Day 8 up to Cycle 21 (cycle length=28 days)
measure: Change from Baseline in Symptomatic Treatment Toxicities as Assessed by National Cancer Institute Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE)
timeFrame: From Day 1 up to Cycle 21 (cycle length=28 days)
Other outcomes:
Locations:
city: Springdale
country: United States
facility: Highlands Oncology Group.
state: Arkansas
city: Duarte
country: United States
facility: City of Hope Cancer Center
state: California
city: Riverside
country: United States
facility: Kaiser Permanente - Riverside
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center Lombardi Cancer Center
state: District of Columbia
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Cancer Center Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: MSK Monmouth
state: New Jersey
city: Montvale
country: United States
facility: MSK Bergen
state: New Jersey
city: Commack
country: United States
facility: MSK Commack
state: New York
city: Harrison
country: United States
facility: MSK Westchester
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: MSK Nassau
state: New York
city: Portland
country: United States
facility: Providence Portland Medical Ctr
state: Oregon
city: Pittsburgh
country: United States
facility: AHN Cancer Institute ? Allegheny General Hospital
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Buenos Aires
country: Argentina
facility: Instituto Alexander Fleming
city: Buenos Aires
country: Argentina
facility: Hospital Britanico
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital Italiano
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: St Albans
country: Australia
facility: Sunshine Hospital
state: Victoria
city: Gent
country: Belgium
facility: UZ Gent
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Namur
country: Belgium
facility: Clinique Ste-Elisabeth
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Lille
country: France
facility: Hopital Claude Huriez
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Berlin
country: Germany
facility: Vivantes Klinikum Am Urban
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf;Urologische Klinik
city: Essen
country: Germany
facility: Uniklinik Essen
city: Hamburg
country: Germany
facility: Uniklinik-Eppendorf
city: Heidelberg
country: Germany
facility: Uniklinikum Heidelberg
city: Herne
country: Germany
facility: Marien Hospital Herne
city: Jena
country: Germany
facility: Universitätsklinikum Jena, Urologische Klinik und Poliklinik
city: München
country: Germany
facility: Klinikum rechts der Isar der TU München
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Athens
country: Greece
facility: Alexandras Hospital
city: Athens
country: Greece
facility: Attikon University General Hospital
city: Thessaloniki
country: Greece
facility: Theageneio Hospital
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Irccs Fondazione G. Pascale
state: Campania
city: Bologna
country: Italy
facility: AZ.Osp S. Orsola ? Malpighi-Reparto di Oncologia Medica
state: Emilia-Romagna
city: Roma
country: Italy
facility: IFO - Istituto Regina Elena
state: Lazio
city: Bergamo
country: Italy
facility: Asst Papa Giovanni XXIII
state: Lombardia
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Lombardia
city: Orbassano
country: Italy
facility: A.O. Universitaria S. Luigi Gonzaga
state: Piemonte
city: Bari
country: Italy
facility: A.O. Universitaria Ospedale Consorziale Policlinico Di Bari
state: Puglia
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto - IRCCS
state: Veneto
city: Verona
country: Italy
facility: A.O.U di Verona Policlinico G.B. Rossi
state: Veneto
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara Fray Antonio Alcalde
state: Jalisco
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: St. Antonius locatie Leidsche Rijn
city: Lørenskog
country: Norway
facility: Akershus universitetssykehus
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. Franciszka ?ukaszczyka
city: Koszalin
country: Poland
facility: Szpital Wojewodzki im. M. Kopernika w Koszalinie
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli
city: Olsztyn
country: Poland
facility: Szpital Kliniczny Ministerstwa Spraw Wewn?trznych i Administracji z Warmi?sko-Mazurskim Centrum Onkologii w Olsztynie
city: Radom
country: Poland
facility: Radomskie Centrum Onkologii
city: Skórzewo
country: Poland
facility: AIDPORT Sp. z o. o.
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie
city: Sant Andreu de La Barca
country: Spain
facility: Vall d'Hebron Institute of Oncology (VHIO), Barcelona
state: Barcelona
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Islas Baleares
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS)
state: LA Coruna
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Instituto Valenciano Oncologia
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Lund
country: Sweden
facility: Skånes Onkologiska Klinik, Universitetssjukhuset
city: Kaohisung
country: Taiwan
facility: Chang Gung Medical Foundation - Kaohsiung
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan Uni Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
city: London
country: United Kingdom
facility: Barts & London School of Med;Medical Oncology
city: Preston
country: United Kingdom
facility: Royal Preston Hosptial
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: