Clinical trial NCT02458638: A Study of Atezolizumab in Advanced Solid Tumors
Official title: An Open-Label, Multicohort, Phase II Study of Atezolizumab in Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tumors
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-06-01
Enrollment: 474
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary efficacy objective for this study is to evaluate non-progression rate (NPR) at 18 weeks in participants with advanced solid tumors treated with atezolizumab, defined as the percentage of participants with complete response (CR), partial response (PR), or stable disease (SD) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1, or according to disease-specific criteria for prostate cancer and malignant pleural mesothelioma.


Eligibility criteria: Inclusion Criteria:

* Histologically documented advanced solid tumors that meet protocol-defined cohort specifications, have progressive disease at study entry, and have received at least one line of prior systemic therapy or for which no alternative therapy to prolong survival exists
* Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (preferred) or in freshly cut and unstained slides (exceptional cases) with an associated pathology report for central testing
* Measurable disease as defined by RECIST v1.1 or disease-specific criteria for prostate cancer and malignant pleural mesothelioma
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Negative serum pregnancy test result within 14 days prior to study drug among women of childbearing potential
* Life expectancy \> 3 months

Exclusion Criteria:

* Malignancies other than disease under study within 5 years prior to Day 1 of Cycle 1 except those with a negligible risk of metastasis or death
* Uncontrolled tumor-related pain
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures \>/=1 time per month
* History of asymptomatic or symptomatic central nervous system (CNS) metastasis
* Leptomeningeal disease
* Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated but without evidence that disease has been clinically stable for \>/=2 weeks prior to Day 1 of Cycle 1
* Pregnant and lactating women
* Significant cardiovascular disease within 3 months prior to Day 1 of Cycle 1
* Severe infection within 4 weeks prior to Day 1 of Cycle 1
* Oral or IV antibiotics within 2 weeks prior to Day 1 of Cycle 1
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation
* History of autoimmune disease except treated/stable hypothyroidism, Type 1 diabetes mellitus, and protocol-specified dermatologic conditions
* Active tuberculosis
* Signs or symptoms of infection within 2 weeks prior to Day 1 of Cycle 1
* Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, or anti-programmed cell death-1 (PD-1) or anti-PD-L1 therapeutic antibodies
* Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to Day 1 of Cycle 1, or anticipated requirement for systemic immunosuppressive medications during the trial

Primary outcomes:
measure: Non-progression Rate (NPR) at 18 Weeks
timeFrame: At Week 18
Secondary outcomes:
measure: NPR at 24 Weeks
timeFrame: At Week 24
measure: Overall Response Rate (ORR)
timeFrame: Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)
measure: Percentage of Participants by Best Overall Response (BOR)
timeFrame: Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)
measure: Clinical Benefit Rate (CBR)
timeFrame: Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)
measure: Duration of Objective Response (DOR)
timeFrame: Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)
measure: Progression-Free Survival (PFS)
timeFrame: Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)
measure: Time to Progression (TTP)
timeFrame: Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)
measure: Overall Survival (OS)
timeFrame: Baseline until death due to any cause (up to 4.5 years)
measure: Number of Participants With Adverse Events
timeFrame: Baseline up to 4.5 years
measure: Treatment Duration of Atezolizumab
timeFrame: Baseline up to approximately 4.5 years
measure: Mean Number of Doses of Atezolizumab
timeFrame: Baseline up to approximately 4.5 years
measure: Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab
timeFrame: Baseline up to 4.5 years
measure: Serum Concentration of Atezolizumab
timeFrame: Predose and postdose on Day 1 of Cycle 1, predose on Day 1 of Cycles 2, 3, 4, 8 (cycle length = 21 days), and every 8 cycles until treatment discontinuation; at follow up (approximately 120 days after last dose) up to approximately 4.5 years
measure: Percentage of Participants by Best Overall Response Based on Modified RECIST v1.1 (mBOR)
timeFrame: Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)
measure: ORR Based on Modified RECIST v1.1
timeFrame: Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)
measure: CBR Based on Modified RECIST v1.1
timeFrame: Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center and Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Graz
country: Austria
facility: LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie
city: Wien
country: Austria
facility: Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Chemotherapie & Infektionskrankhei
city: Rio de Janeiro
country: Brazil
facility: INCA 1- Instituto Nacional de Câncer X
state: RJ
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas - UFRGS
state: RS
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: SP
city: Vancouver
country: Canada
facility: BCCA-Vancouver Cancer Centre
state: British Columbia
city: Toronto
country: Canada
facility: University Health Network; Princess Margaret Hospital; Medical Oncology Dept
state: Ontario
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital; Kræftafdelingen
city: Herlev
country: Denmark
facility: Herlev Hospital; Afdeling for Kræftbehandling
city: Odense C
country: Denmark
facility: Odense Universitetshospital, Onkologisk Afdeling, Klinisk Forsknings Enhed
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital; Dept of Oncology
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lyon
country: France
facility: Centre Leon Berard; Departement Oncologie Medicale
city: Paris
country: France
facility: Hopital Saint Louis, Service D Oncologie Medicale
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Hamburg
country: Germany
facility: Uniklinik-Eppendorf; Zentren F. Innere Medizin-Klinik U. Poliklinik
city: Heidelberg
country: Germany
facility: Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen
city: Trier
country: Germany
facility: Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie
city: Dublin
country: Ireland
facility: St Vincent'S Uni Hospital; Medical Oncology
city: Dublin
country: Ireland
facility: St James' Hospital; Cancer Clinical Trials Office
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
state: Campania
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
state: Lombardia
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica
state: Toscana
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Bergen
country: Norway
facility: Haukeland Universitetssjukehus; Klinisk forskningspost
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF; Radiumhospitalet
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii w Bydgoszczy
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. M.Sklodowskiej-Curie; Klinika Now. Tkanek Miekkich,Kosci i Czer.
city: Moscow
country: Russian Federation
facility: Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy
city: Saint-Petersburg
country: Russian Federation
facility: S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra; Servicio de Oncologia
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Fribourg
country: Switzerland
facility: Freiburger Spital; Onkologie
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen; Onkologie/Hämatologie
city: Edirne
country: Turkey
facility: Trakya University Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology
city: Istanbul
country: Turkey
facility: Prof. Dr. Cemil Tascioglu City Hospital; Med Onc
city: Sihhiye/Ankara
country: Turkey
facility: Hacettepe Uni Medical Faculty Hospital; Oncology Dept
city: Bebington
country: United Kingdom
facility: Clatterbridge Cancer Centre
city: Southampton
country: United Kingdom
facility: Southampton General Hospital; Medical Oncology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Tabernero J, Andre F, Blay JY, Bustillos A, Fear S, Ganta S, Jaeger D, Maio M, Mileshkin L, Melero I. Phase II multicohort study of atezolizumab monotherapy in multiple advanced solid cancers. ESMO Open. 2022 Apr;7(2):100419. doi: 10.1016/j.esmoop.2022.100419. Epub 2022 Mar 16.