Clinical trial NCT03498521: A Phase II Randomized Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site
Official title: A Phase II, Randomized, Active-Controlled, Multi-Center Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Guided by Genomic Profiling Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site Who Have Received Three Cycles of Platinum Doublet Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer of Unknown Primary Site
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Foundation Medicine
First posted: 2018-04-13
Enrollment: 528
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: This study will compare the efficacy and safety of molecularly-guided therapy versus standard platinum-containing chemotherapy in participants with poor-prognosis cancer of unknown primary site (CUP; non-specific subset) who have achieved disease control after 3 cycles of first-line platinum based induction chemotherapy.


Eligibility criteria: Inclusion Criteria:

* Histologically-confirmed unresectable cancer of unknown primary site (CUP) diagnosed according to criteria defined in the 2015 European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for CUP
* No prior lines of systemic therapy for the treatment of CUP
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Candidate for platinum-based chemotherapy (according to the reference information for the intended chemotherapy)
* At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
* Formalin-Fixed Paraffin-Embedded (FFPE) tumor tissue sample \</= 4 months old that is expected to be sufficient for generation of a comprehensive genomic profile at a central reference pathology laboratory

Exclusion Criteria:

* Squamous cell CUP
* Participants who can be assigned to a specific subset of CUP for which a specific treatment is recommended by the 2015 ESMO Clinical Practice Guidelines for CUP or with a clinical and IHC profile indicative of a specific primary tumor (favorable prognosis CUP subsets): Poorly differentiated carcinoma with midline distribution; women with papillary adenocarcinoma of the peritoneal cavity; women with adenocarcinoma involving only the axillary lymph nodes; squamous cell carcinoma of the cervical lymph nodes; poorly differentiated neuroendocrine tumors; men with blastic bone metastases and elevated prostate-specific antigen (PSA); participants with a single, small, potentially resectable tumor; colon cancer-type CUP, including participants with a CK7 negative, CK20 positive, CDX-2 positive immunohistochemistry profile; CK7-positive, CK20-negative and TTF-1 positive tumors in a context suggestive of lung adenocarcinoma or thyroid cancer; IHC profile definitely indicative of breast cancer OR an IHC profile indicative of breast cancer and either a history of breast cancer or lymph nodes in the drainage areas of the breast; high-grade serious carcinoma histology and elevated CA125 tumor marker and/or a mass in the gynecological tract or any tumor mass or lymph node in the abdominal cavity; IHC profile suggestive of renal cell carcinoma and renal lesions, with a Bosniak classification higher than IIF; IHC profile compatible with cholangiocarcinoma or pancreatobiliary (or upper gastrointestinal carcinoma) AND 1 or 2 liver lesions without extrahepatic disease or with only pulmonary metastases and/or lymph nodes in the drainage areas of the liver
* Known presence of brain or spinal cord metastasis (including metastases that have been irradiated only)
* Histology and immunohistology profiles (per 2015 ESMO guidelines) that are not adenocarcinoma or poorly differentiated carcinoma/adenocarcinoma
* History or known presence of leptomeningeal disease
* Known human immunodeficiency virus (HIV) infection
* Significant cardiovascular disease
* Prior allogeneic stem cell or solid organ transplantation
* Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or for up to 7 months after the final dose of treatment

Primary outcomes:
measure: Progression Free Survival (PFS) as Assessed by the Investigator According to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1)
timeFrame: From randomization to the first occurrence of disease progression or death from any cause, until 330 PFS events were observed (approx. 4.3 years for MGT Cat 1 and 3.4 years for Chemotherapy Cat 1).
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization to death from any cause (approx. 4 years)
measure: Objective Response Rate (ORR)
timeFrame: Two consecutive occurrences of complete or partial response >/=4 weeks apart (up to approximately 4 months)
measure: Duration of Response (DOR)
timeFrame: From the first documentation of a complete response (CR) or partial response (PR) to disease progression or death from any cause, whichever occurs first (up to approximately 4 years)
measure: Disease Control Rate (DCR)
timeFrame: From randomization to death from any cause, through the end of study (approximately 4 years)
Other outcomes:
Locations:
city: Blacktown
country: Australia
facility: Blacktown Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: GenesisCare North Shore
state: New South Wales
city: South Brisbane
country: Australia
facility: Icon Cancer Foundation
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
city: Graz
country: Austria
facility: Lkh-Univ. Klinikum Graz
city: Salzburg
country: Austria
facility: Lkh Salzburg - Univ. Klinikum Salzburg
city: Wien
country: Austria
facility: Medizinische Universität Wien
city: Salvador
country: Brazil
facility: Hospital Sao Rafael - HSR
state: Bahia
city: Barretos
country: Brazil
facility: Hospital de Cancer de Barretos
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cancer - INCa
city: Sofia
country: Bulgaria
facility: MHAT Nadezhda
city: Sofia
country: Bulgaria
facility: MBAL Serdika EOOD
city: Recoleta
country: Chile
facility: Bradford Hill Centro de Investigaciones Clinicas
city: Temuco
country: Chile
facility: James Lind Centro de Investigación Del Cáncer
city: Bogota
country: Colombia
facility: Clinica del Country
city: Bogota
country: Colombia
facility: Inst. Nacional de Cancerologia
city: Monteria
country: Colombia
facility: Oncomedica S.A.
city: Zagreb
country: Croatia
facility: Clinical Hospital Centre Zagreb
city: Brno
country: Czechia
facility: Masarykuv onkologicky ustav
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Praha 2
country: Czechia
facility: Fakultni Poliklinika Vseobecne Fakultni Niemocnice
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital
city: København Ø
country: Denmark
facility: Rigshospitalet
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre, Oncology and hematology Clinic
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Angers
country: France
facility: Ico - Paul Papin
city: Besançon
country: France
facility: CHRU Besançon
city: Bordeaux
country: France
facility: Institut Bergonie
city: Caen
country: France
facility: CRLCC-Francois Baclesse
city: Clermont-ferrand
country: France
facility: Centre Jean Perrin Centre Regional de Lutte Contre Le Cancer D auvergne
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille Cedex 09
country: France
facility: Institut Paoli-Calmettes
city: Montpellier
country: France
facility: Institut régional du Cancer Montpellier
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institut Curie
city: Pierre-Benite (Lyon)
country: France
facility: CHU Lyon - Centre Hospitalier Lyon Sud
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Strasbourg
country: France
facility: CHU Strasbourg Hôpital Hautepierre
city: Suresnes
country: France
facility: Hopital Foch
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg
city: Berlin
country: Germany
facility: Charité-Universitätsm. Berlin
city: Dachau
country: Germany
facility: Onkologisches Zentrum - Onkologie Dachau
city: Dresden
country: Germany
facility: Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
city: Essen
country: Germany
facility: Kliniken Essen-Mitte, Evang. Huyssens-Stiftung, Klinik für Internistische Onkologie / Haematologie
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt, UCT
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Heilbronn
country: Germany
facility: SLK-Kliniken Heilbronn GmbH;Klinik für Innere Medizin III
city: Jena
country: Germany
facility: Universitätsklinikum Jena, Klinik für Innere Medizin II
city: Mannheim
country: Germany
facility: Klinikum Mannheim III. Medizinische Klinik
city: München
country: Germany
facility: Klinikum der LMU München, Campus Großhadern, Krebszentrum München
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Medizinische Klinik A, Translationale Onkologie
city: Oldenburg / Holstein
country: Germany
facility: RED-Oncology GmbH
city: Athens
country: Greece
facility: Anticancer Hospital Ag Savas
city: Athens
country: Greece
facility: IASO General Hospital of Athens
city: Heraklion
country: Greece
facility: Univ General Hosp Heraklion
city: Ioannina
country: Greece
facility: Uni Hospital of Ioannina
city: Thessaloniki
country: Greece
facility: Theagenio Anticancer Hospital
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Budapest
country: Hungary
facility: Budapesti Uzsoki Utcai Kórház
city: Kecskemét
country: Hungary
facility: Bács-Kiskun Vármegyei Oktatókórház
city: Dublin
country: Ireland
facility: St Vincent'S Uni Hospital
city: Waterford
country: Ireland
facility: Waterford Regional Hospital
city: Petach Tikva
country: Israel
facility: Rabin MC
city: Ramat Gan
country: Israel
facility: Chaim Sheba medical center, Oncology division
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Ctr
city: Pisa
country: Italy
facility: U. O. Oncologia Medica, Ospedale Santa Chiara
state: Basilicata
city: Catanzaro
country: Italy
facility: Policlinico Univ. - A.O. Mater Domini
state: Calabria
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
state: Campania
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova
state: Emilia-Romagna
city: Bergamo
country: Italy
facility: Asst Papa Giovanni XXIII
state: Lombardia
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda)
state: Lombardia
city: Padova
country: Italy
facility: IRCCS Istituto Oncologico Veneto (IOV)
state: Veneto
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Riga
country: Latvia
facility: Riga East Clinical University Hospital Latvian Oncology Centre
city: CD Mexico
country: Mexico
facility: Health Pharma Professional Research
state: Mexico CITY (federal District)
city: Monterrey
country: Mexico
facility: AVIX Investigación Clínica S.C
state: Nuevo LEON
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Venlo
country: Netherlands
facility: Ziekenhuis VieCuri Medisch Centrum
city: Kristiansand
country: Norway
facility: Sørlandet Sykehus Kristiansand
city: Lørenskog
country: Norway
facility: Akershus universitetssykehus HF
city: Oslo
country: Norway
facility: Oslo universitetssykehus HF, Ullevål, Kreftsenteret
city: Lima
country: Peru
facility: Instituto Nacional de Enfermedades Neoplasicas
city: Lima
country: Peru
facility: Oncosalud Sac
city: Kraków
country: Poland
facility: Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii
city: Porto
country: Portugal
facility: IPO do Porto
city: Cluj Napoca
country: Romania
facility: Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj Napoca
city: Craiova
country: Romania
facility: Centrul de Oncologie Sfantul Nectarie
city: Iasi
country: Romania
facility: Institutul Regional de Oncologie Iasi
city: Timi?oara
country: Romania
facility: Oncocenter Timisoara
city: Sant Joan Despí
country: Spain
facility: Hospital Sant Joan Despi- Moises Broggi
state: Barcelona
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
state: Navarra
city: Vigo
country: Spain
facility: Complexo Hospitalario de Vigo. Hospital Álvaro Cunqueiro
state: Pontevedra
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial
city: Barcelona
country: Spain
facility: Institut Catala d Oncologia Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Basel
country: Switzerland
facility: Universitaetsspital Basel
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital;Medicine/Oncology
city: Bangkok
country: Thailand
facility: Faculty of Med. Siriraj Hosp.
city: Adana
country: Turkey
facility: Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty
city: Ankara
country: Turkey
facility: Ankara Oncology Hospital
city: Antalya
country: Turkey
facility: Akdeniz University Medical Faculty
city: Edirne
country: Turkey
facility: Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpa?a-Cerrahpa?a Medical Faculty
city: Kar?iyaka
country: Turkey
facility: ?zmir Medical Point
city: S?hhiye, Ankara
country: Turkey
facility: Hacettepe Uni Medical Faculty Hospital
city: Bath
country: United Kingdom
facility: Royal United Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Torquay
country: United Kingdom
facility: Torbay Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: