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
- Conditions
- Cancer of Unknown Primary Site
- Interventions
- Registration Number
- NCT03498521
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 528
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Molecularly-Guided Therapy Trastuzumab Subcutaneous (SC) Participants will be assigned to molecularly-guided therapy based on genomic profile. Platinum-Based Chemotherapy Trastuzumab Subcutaneous (SC) Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel). Molecularly-Guided Therapy Alectinib Participants will be assigned to molecularly-guided therapy based on genomic profile. Molecularly-Guided Therapy Vismodegib Participants will be assigned to molecularly-guided therapy based on genomic profile. Molecularly-Guided Therapy Erlotinib Participants will be assigned to molecularly-guided therapy based on genomic profile. Molecularly-Guided Therapy Olaparib Participants will be assigned to molecularly-guided therapy based on genomic profile. Molecularly-Guided Therapy Bevacizumab Participants will be assigned to molecularly-guided therapy based on genomic profile. Molecularly-Guided Therapy Cobimetinib Participants will be assigned to molecularly-guided therapy based on genomic profile. Molecularly-Guided Therapy Vemurafenib Participants will be assigned to molecularly-guided therapy based on genomic profile. Molecularly-Guided Therapy Pertuzumab Participants will be assigned to molecularly-guided therapy based on genomic profile. Molecularly-Guided Therapy Paclitaxel Participants will be assigned to molecularly-guided therapy based on genomic profile. Molecularly-Guided Therapy Atezolizumab Participants will be assigned to molecularly-guided therapy based on genomic profile. Molecularly-Guided Therapy Ivosidenib Participants will be assigned to molecularly-guided therapy based on genomic profile. Molecularly-Guided Therapy Entrectinib Participants will be assigned to molecularly-guided therapy based on genomic profile. Molecularly-Guided Therapy Pemigatinib Participants will be assigned to molecularly-guided therapy based on genomic profile. Platinum-Based Chemotherapy Pertuzumab Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel). Platinum-Based Chemotherapy Carboplatin Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel). Platinum-Based Chemotherapy Paclitaxel Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel). Platinum-Based Chemotherapy Cisplatin Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel). Platinum-Based Chemotherapy Gemcitabine Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel). Molecularly-Guided Therapy Ipatasertib Participants will be assigned to molecularly-guided therapy based on genomic profile.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) as Assessed by the Investigator According to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1) 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). This efficacy objective was to evaluate the efficacy of MGT vs platinum chemotherapy in term of PFS in participants with CUP whose best response to 3 cycles of platinum induction chemotherapy was assessed CR, PR, or SD.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) From randomization to death from any cause (approx. 4 years) Objective Response Rate (ORR) Two consecutive occurrences of complete or partial response >/=4 weeks apart (up to approximately 4 months) Duration of Response (DOR) 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) Disease Control Rate (DCR) From randomization to death from any cause, through the end of study (approximately 4 years)
Trial Locations
- Locations (130)
Centre Antoine Lacassagne
🇫🇷Nice, France
Institut Curie
🇫🇷Paris, France
CHU Lyon - Centre Hospitalier Lyon Sud
🇫🇷Pierre-Benite (Lyon), France
Centre Eugene Marquis
🇫🇷Rennes, France
CHU Strasbourg Hôpital Hautepierre
🇫🇷Strasbourg, France
Hopital Foch
🇫🇷Suresnes, France
Blacktown Hospital
🇦🇺Blacktown, New South Wales, Australia
GenesisCare North Shore
🇦🇺St Leonards, New South Wales, Australia
Icon Cancer Foundation
🇦🇺South Brisbane, Queensland, Australia
Lkh-Univ. Klinikum Graz
🇦🇹Graz, Austria
Lkh Salzburg - Univ. Klinikum Salzburg
🇦🇹Salzburg, Austria
Medizinische Universität Wien
🇦🇹Wien, Austria
Hospital Sao Rafael - HSR
🇧🇷Salvador, Bahia, Brazil
Hospital de Cancer de Barretos
🇧🇷Barretos, São Paulo, Brazil
Institut Gustave Roussy
🇫🇷Villejuif, France
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Universitaetsspital Basel
🇨🇭Basel, Switzerland
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Clínic i Provincial
🇪🇸Barcelona, Spain
Institut Catala d Oncologia Hospital Duran i Reynals
🇪🇸Barcelona, Spain
Hospital Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Clinico Universitario Virgen de la Victoria
🇪🇸Malaga, Spain
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
Peter MacCallum Cancer Center
🇦🇺Melbourne, Victoria, Australia
Instituto do Cancer do Estado de Sao Paulo - ICESP
🇧🇷Sao Paulo, São Paulo, Brazil
Instituto Nacional de Cancer - INCa
🇧🇷Rio de Janeiro, Brazil
MHAT Nadezhda
🇧🇬Sofia, Bulgaria
MBAL Serdika EOOD
🇧🇬Sofia, Bulgaria
Bradford Hill Centro de Investigaciones Clinicas
🇨🇱Recoleta, Chile
James Lind Centro de Investigación Del Cáncer
🇨🇱Temuco, Chile
Clinica del Country
🇨🇴Bogota, Colombia
Inst. Nacional de Cancerologia
🇨🇴Bogota, Colombia
Oncomedica S.A.
🇨🇴Monteria, Colombia
Clinical Hospital Centre Zagreb
🇭🇷Zagreb, Croatia
Masarykuv onkologicky ustav
🇨🇿Brno, Czechia
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Fakultni Poliklinika Vseobecne Fakultni Niemocnice
🇨🇿Praha 2, Czechia
Aarhus Universitetshospital
🇩🇰Aarhus N, Denmark
Rigshospitalet
🇩🇰København Ø, Denmark
North Estonia Medical Centre, Oncology and hematology Clinic
🇪🇪Tallinn, Estonia
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
Tampere University Hospital
🇫🇮Tampere, Finland
Ico - Paul Papin
🇫🇷Angers, France
CHRU Besançon
🇫🇷Besançon, France
Institut Bergonie
🇫🇷Bordeaux, France
CRLCC-Francois Baclesse
🇫🇷Caen, France
Centre Jean Perrin Centre Regional de Lutte Contre Le Cancer D auvergne
🇫🇷Clermont-ferrand, France
Centre Leon Berard
🇫🇷Lyon, France
Institut Paoli-Calmettes
🇫🇷Marseille Cedex 09, France
Institut régional du Cancer Montpellier
🇫🇷Montpellier, France
Universitätsklinikum Augsburg
🇩🇪Augsburg, Germany
Charité-Universitätsm. Berlin
🇩🇪Berlin, Germany
Onkologisches Zentrum - Onkologie Dachau
🇩🇪Dachau, Germany
Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
🇩🇪Dresden, Germany
Kliniken Essen-Mitte, Evang. Huyssens-Stiftung, Klinik für Internistische Onkologie / Haematologie
🇩🇪Essen, Germany
Universitätsklinikum Frankfurt, UCT
🇩🇪Frankfurt, Germany
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
SLK-Kliniken Heilbronn GmbH;Klinik für Innere Medizin III
🇩🇪Heilbronn, Germany
Universitätsklinikum Jena, Klinik für Innere Medizin II
🇩🇪Jena, Germany
Klinikum Mannheim III. Medizinische Klinik
🇩🇪Mannheim, Germany
Klinikum der LMU München, Campus Großhadern, Krebszentrum München
🇩🇪München, Germany
Universitätsklinikum Münster, Medizinische Klinik A, Translationale Onkologie
🇩🇪Münster, Germany
RED-Oncology GmbH
🇩🇪Oldenburg / Holstein, Germany
Anticancer Hospital Ag Savas
🇬🇷Athens, Greece
IASO General Hospital of Athens
🇬🇷Athens, Greece
Univ General Hosp Heraklion
🇬🇷Heraklion, Greece
Uni Hospital of Ioannina
🇬🇷Ioannina, Greece
Theagenio Anticancer Hospital
🇬🇷Thessaloniki, Greece
Orszagos Onkologiai Intezet
🇭🇺Budapest, Hungary
Budapesti Uzsoki Utcai Kórház
🇭🇺Budapest, Hungary
Bács-Kiskun Vármegyei Oktatókórház
🇭🇺Kecskemét, Hungary
St Vincent'S Uni Hospital
🇮🇪Dublin, Ireland
Waterford Regional Hospital
🇮🇪Waterford, Ireland
Rabin MC
🇮🇱Petach Tikva, Israel
Chaim Sheba medical center, Oncology division
🇮🇱Ramat Gan, Israel
Tel Aviv Sourasky Medical Ctr
🇮🇱Tel Aviv, Israel
U. O. Oncologia Medica, Ospedale Santa Chiara
🇮🇹Pisa, Basilicata, Italy
Policlinico Univ. - A.O. Mater Domini
🇮🇹Catanzaro, Calabria, Italy
Istituto Nazionale Tumori Fondazione G. Pascale
🇮🇹Napoli, Campania, Italy
Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Emilia-Romagna, Italy
Asst Papa Giovanni XXIII
🇮🇹Bergamo, Lombardia, Italy
Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda)
🇮🇹Milano, Lombardia, Italy
IRCCS Istituto Oncologico Veneto (IOV)
🇮🇹Padova, Veneto, Italy
National Cancer Center Hospital East
🇯🇵Chiba, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Riga East Clinical University Hospital Latvian Oncology Centre
🇱🇻Riga, Latvia
Health Pharma Professional Research
🇲🇽CD Mexico, Mexico CITY (federal District), Mexico
AVIX Investigación Clínica S.C
🇲🇽Monterrey, Nuevo LEON, Mexico
Erasmus MC
🇳🇱Rotterdam, Netherlands
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
Ziekenhuis VieCuri Medisch Centrum
🇳🇱Venlo, Netherlands
Sørlandet Sykehus Kristiansand
🇳🇴Kristiansand, Norway
Akershus universitetssykehus HF
🇳🇴Lørenskog, Norway
Oslo universitetssykehus HF, Ullevål, Kreftsenteret
🇳🇴Oslo, Norway
Instituto Nacional de Enfermedades Neoplasicas
🇵🇪Lima, Peru
Oncosalud Sac
🇵🇪Lima, Peru
Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii
🇵🇱Kraków, Poland
IPO do Porto
🇵🇹Porto, Portugal
Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj Napoca
🇷🇴Cluj Napoca, Romania
Centrul de Oncologie Sfantul Nectarie
🇷🇴Craiova, Romania
Institutul Regional de Oncologie Iasi
🇷🇴Iasi, Romania
Oncocenter Timisoara
🇷🇴Timi?oara, Romania
Hospital Sant Joan Despi- Moises Broggi
🇪🇸Sant Joan Despí, Barcelona, Spain
Complejo Hospitalario de Navarra
🇪🇸Pamplona, Navarra, Spain
Complexo Hospitalario de Vigo. Hospital Álvaro Cunqueiro
🇪🇸Vigo, Pontevedra, Spain
UniversitätsSpital Zürich
🇨🇭Zürich, Switzerland
Ramathibodi Hospital;Medicine/Oncology
🇹🇭Bangkok, Thailand
Faculty of Med. Siriraj Hosp.
🇹🇭Bangkok, Thailand
Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital
🇹🇷Adana, Turkey
Ankara University Medical Faculty
🇹🇷Ankara, Turkey
Ankara Oncology Hospital
🇹🇷Ankara, Turkey
Akdeniz University Medical Faculty
🇹🇷Antalya, Turkey
Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
🇹🇷Edirne, Turkey
Istanbul University Cerrahpa?a-Cerrahpa?a Medical Faculty
🇹🇷Istanbul, Turkey
?zmir Medical Point
🇹🇷Kar?iyaka, Turkey
Hacettepe Uni Medical Faculty Hospital
🇹🇷S?hhiye, Ankara, Turkey
Royal United Hospital
🇬🇧Bath, United Kingdom
Velindre Cancer Centre
🇬🇧Cardiff, United Kingdom
Western General Hospital
🇬🇧Edinburgh, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Christie Hospital NHS Trust
🇬🇧Manchester, United Kingdom
Freeman Hospital
🇬🇧Newcastle upon Tyne, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Torbay Hospital
🇬🇧Torquay, United Kingdom