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

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



Sponsors

Lead Sponsor


Collaborators



Source

Hoffmann-La Roche

Oversight Info

Has Dmc

Yes

Is Fda Regulated Drug

Yes

Is Fda Regulated Device

No

Is Us Export

Yes


Brief Summary

This study will compare the efficacy and safety of molecularly-guided therapy versus standard
platinum-containing chemotherapy in participants with cancer of unknown primary site (CUP;
non-specific subset) who have achieved disease control after 3 cycles of first-line platinum
doublet induction chemotherapy.

Overall Status

Recruiting

Start Date

2018-07-10

Completion Date

2022-04-16

Primary Completion Date

2022-04-16

Phase

Phase 2

Study Type

Interventional

Primary Outcome

Measure

Time Frame

Progression Free Survival (PFS1)
Randomization to the first occurrence of disease progression as assessed by the investigator according to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1) or death from any cause, through the end of study (approximately 48 months)

Secondary Outcome

Measure

Time Frame

Overall Survival (OS)
Randomization to death from any cause, through the end of study (approximately 48 months)
Overall Response Rate (ORR1)
Two consecutive occurrences of complete or partial response >/=4 weeks apart
Duration of Clinical Benefit (DCB1)
From the first occurrence of a complete response (CR), partial response (PR), or stable disease (SD) after randomization, until disease progression or death from any cause, through the end of study (approximately 48 months)
Percentage of Participants with Adverse Events (AE)
From baseline through the end of study (approximately 48 months)

Enrollment

790

Condition


Intervention

Intervention Type

Drug

Intervention Name


Description

Alectinib will be administered orally at the label-recommended dose (600 mg) twice daily until disease progression or unacceptable toxicity, through the end of the study (approximately 48 months).

Arm Group Label

Molecularly-Guided Therapy


Intervention Type

Drug

Intervention Name


Description

Vismodegib will be administered orally at the label-recommended dose (150 mg) once daily until disease progression or unacceptable toxicity, through the end of the study (approximately 48 months).

Arm Group Label

Molecularly-Guided Therapy


Intervention Type

Drug

Intervention Name


Description

Ipatasertib will be administered orally at the label-recommended dose (400 mg) once daily until disease progression or unacceptable toxicity, through the end of the study (approximately 48 months).

Arm Group Label

Molecularly-Guided Therapy


Intervention Type

Drug

Intervention Name


Description

Olaparib will be administered orally at the label-recommended dose (400 mg) twice daily until disease progression or unacceptable toxicity, through the end of the study (approximately 48 months).

Arm Group Label

Molecularly-Guided Therapy


Intervention Type

Drug

Intervention Name


Description

Erlotinib will be administered orally in combination with Bevacizumab at the label recommended dose (150 mg) once daily until disease progression or unacceptable toxicity, through the end of the study (approximately 48 months)

Arm Group Label

Molecularly-Guided Therapy


Intervention Type

Drug

Intervention Name


Description

Bevacizumab will be administered intravenously at 15mg/kg every 3 weeks in combination with Erlotinib until disease progression or unacceptable toxicity, through the end of the study (approximately 48 months)

Arm Group Label

Molecularly-Guided Therapy


Intervention Type

Drug

Intervention Name


Description

Vemurafenib will be administered orally, 960 mg twice daily, in combination with Cobimetinib, until disease progression or unacceptable toxicity, through the end of the study (approximately 48 months)

Arm Group Label

Molecularly-Guided Therapy


Intervention Type

Drug

Intervention Name


Description

Cobimetinib will be administered orally, 60mg once daily, in combination with Vemurafenib, until disease progression or unacceptable toxicity, through the end of the study (approximately 48 months)

Arm Group Label

Molecularly-Guided Therapy


Intervention Type

Drug

Intervention Name


Description

Trastuzumab will be administered subcutaneously, 600 mg every 3 weeks, in combination with Pertuzumab and chemotherapy, until disease progression or unacceptable toxicity, through the end of the study (approximately 48 months)

Arm Group Label

Molecularly-Guided Therapy

Platinum-Based Chemotherapy



Intervention Type

Drug

Intervention Name


Description

Pertuzumab will be initially be administered intravenously, 840 mg, followed by 420 mg every 3 weeks, in combination with Trastuzumab and chemotherapy, until disease progression or unacceptable toxicity, through the end of the study (approximately 48 months)

Arm Group Label

Molecularly-Guided Therapy

Platinum-Based Chemotherapy



Intervention Type

Drug

Intervention Name


Description

Atezolizumab will be administered intravenously at the label-recommended dose (1200 mg) every 3 weeks until disease progression or unacceptable toxicity, through the end of the study (approximately 48 months).

Arm Group Label

Molecularly-Guided Therapy


Intervention Type

Drug

Intervention Name


Description

Carboplatin will be administered intravenously at the area under the curve (AUC) dose once every 3 weeks in combination with Paclitaxel or Gemcitabine, until disease progression or unacceptable toxicity, for up to 6 cycles (Cycle = 21 days).

Arm Group Label

Platinum-Based Chemotherapy


Intervention Type

Drug

Intervention Name


Description

Paclitaxel will be administered intravenously, 175 mg/m^2, once every 3 weeks in combination with Carboplatin, until disease progression or unacceptable toxicity, for up to 6 cycles (Cycle = 21 days).

Arm Group Label

Platinum-Based Chemotherapy


Intervention Type

Drug

Intervention Name


Description

Cisplatin will be administered intravenously, 60-75 mg/m^2, in combination with Gemcitabine or Paclitaxel, once every three weeks, until disease progression or unacceptable toxicity, for up to 6 cycles (Cycle = 21 days).

Arm Group Label

Platinum-Based Chemotherapy


Intervention Type

Drug

Intervention Name


Description

Gemcitabine will be administered intravenously, 1000 mg/m^2, twice every three weeks, in combination with Cisplatin or Carboplatin, until disease progression or unacceptable toxicity, for up to 6 cycles (Cycle = 21 days).

Arm Group Label

Platinum-Based Chemotherapy



Eligibility

Criteria

Inclusion Criteria:

- Histologically-confirmed cancer of unknown primary site (CUP)(non-specific subset)
according to criteria from the European Society for Medical Oncology, version 1 (ESMO
v1)

- Each patient must provide a blood sample for genomic profiling

- 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 doublet chemotherapy (according to the reference
information for the intended doublet therapy)

- 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 that is sufficient for
generation of a comprehensive genomic profile at a central reference pathology
laboratory

Exclusion Criteria:

- Squamous cell CUP

- 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 24 months after the last dose of study treatment

Gender

All

Minimum Age

18 Years

Maximum Age

N/A

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Clinical Trials
Study Director
Hoffmann-La Roche

Overall Contact

Last Name

Reference Study ID Number: MX39795 www.roche.com/about_roche/roche_worldwide.htm

Phone

888-662-6728 (U.S. Only)

Email



Location

Facility

Status

Blacktown Hospital
Blacktown New South Wales NSW 2148 Australia
Recruiting
Icon Cancer Foundation
South Brisbane Queensland 4101 Australia
Recruiting
Flinders Medical Centre
Bedford Park South Australia 5042 Australia
Recruiting
Peter MacCallum Cancer Center
Melbourne Victoria 3000 Australia
Recruiting
LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie
Graz 8036 Austria
Not yet recruiting
INCA 1- Instituto Nacional de Câncer
Rio de Janeiro RJ 20231-050 Brazil
Not yet recruiting
Hospital Nossa Senhora da Conceicao
Porto Alegre RS 91350-200 Brazil
Not yet recruiting
Instituto do Cancer do Estado de Sao Paulo - ICESP
Sao Paulo SP 01246-000 Brazil
Not yet recruiting
Complex Oncology Center (COC)-Plovidiv
Plovdiv 4000 Bulgaria
Not yet recruiting
MBAL Serdika EOOD
Sofia 1303 Bulgaria
Not yet recruiting
MHAT Nadezhda
Sofia 1330 Bulgaria
Not yet recruiting
Clinical Hospital Centre Zagreb
Zagreb 10000 Croatia
Not yet recruiting
Masarykuv onkologicky ustav
Brno 656 53 Czechia
Not yet recruiting
Fakultni nemocnice Olomouc; Onkologicka klinika
Olomouc 779 00 Czechia
Not yet recruiting
Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika
Praha 2 128 08 Czechia
Not yet recruiting
North Estonia Medical Centre, Oncology and hematology Clinic; Department of Chemotherapy
Tallinn 13419 Estonia
Recruiting
Helsinki University Central Hospital; Dept of Oncology
Helsinki 00029 Finland
Not yet recruiting
Tampere University Hospital; Dept of Oncology
Tampere 33520 Finland
Recruiting
CHRU Besançon
Besançon 25030 France
Not yet recruiting
Institut Bergonie; Oncologie
Bordeaux 33076 France
Not yet recruiting
CRLCC-Francois Baclesse; Oncologie Médicale
Caen 14076 France
Not yet recruiting
Institut régional du Cancer Montpellier
Montpellier 34298 France
Not yet recruiting
Centre Antoine Lacassagne
Nice 06189 France
Not yet recruiting
CHU Lyon - Centre Hospitalier Lyon Sud
Pierre-Benite (Lyon) 69495 France
Not yet recruiting
Centre Eugene Marquis; Service d'oncologie
Rennes 35042 France
Not yet recruiting
CHU Strasbourg - Hôpital Hautepierre
Strasbourg 67098 France
Not yet recruiting
Service d'Oncologie, Institut Universitaire du Cancer de Toulouse
Toulouse 31059 France
Not yet recruiting
Institut Gustave Roussy
Villejuif 94805 France
Not yet recruiting
Klinikum Augsburg; II. Med. Klinik
Augsburg 86156 Germany
Not yet recruiting
Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.
Berlin 10117 Germany
Not yet recruiting
Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
Dresden 01307 Germany
Not yet recruiting
Universitätsklinikum Düsseldorf; Klinik für Hämatologie, Onkologie und Klinische Immunologie
Düsseldorf 40225 Germany
Not yet recruiting
Kliniken Essen-Mitte, Evang. Huyssens-Stiftung, Klinik für Internistische Onkologie / Haematologie
Essen 45136 Germany
Not yet recruiting
Universitätsklinikum Frankfurt, UCT; Universitäres Centrum für Tumorerkrankungen
Frankfurt 60590 Germany
Not yet recruiting
Universitätsklinikum Hamburg-Eppendorf, Onkologisches Zentrum, Studienzentrale der II. Med. Klinik
Hamburg 20246 Germany
Not yet recruiting
Universitätsklinikum Heidelberg;Innere Medizin V, Hämatologie/Onkologie
Heidelberg 69120 Germany
Not yet recruiting
Universitätsklinikum Jena, Klinik für Innere Medizin II; Hämatologie und Internistische Onkologie
Jena 07740 Germany
Not yet recruiting
UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz; III. Med. Klinik u. Poliklinik
Mainz 55131 Germany
Not yet recruiting
Klinikum Mannheim III. Medizinische Klinik
Mannheim 68167 Germany
Not yet recruiting
Klinikum der LMU München, Campus Großhadern, Krebszentrum München; Comprehensive Cancer Center LMU
München 81377 Germany
Not yet recruiting
ohO - ostholstein ONKOLOGIE; Dres.Gerdt Hübner/Clemens Engels (Oldenburg)/Yael Bonnin-Gruber (Eutin)
Oldenburg / Holstein 23758 Germany
Not yet recruiting
Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine
Athens 115 22 Greece
Not yet recruiting
IASO General Hospital of Athens
Athens 155 62 Greece
Not yet recruiting
Uni Hospital of Ioannina; Oncology Dept.
Ioannina 455 00 Greece
Not yet recruiting
Semmelweis Egyetem; Onkológiai Központ
Budapest 1083 Hungary
Not yet recruiting
Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly
Budapest 1122 Hungary
Not yet recruiting
Uzsoki Utcai Korhaz; Onkoradiológiai Osztály
Budapest 1145 Hungary
Not yet recruiting
Debreceni Egyetem Klinikai Kozpont ; Department of Oncology
Debrecen H4032 Hungary
Not yet recruiting
Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika
Szeged 6720 Hungary
Not yet recruiting
St Vincent'S Uni Hospital; Medical Oncology
Dublin 4 Ireland
Not yet recruiting
Waterford Regional Hospital; Department Of Medical Oncology
Waterford Ireland
Not yet recruiting
U. O. Oncologia Medica, Ospedale Santa Chiara
Pisa Basilicata 56100 Italy
Not yet recruiting
Policlinico Univ. - A.O. Mater Domini; U.O. Di Oncoematologia
Catanzaro Calabria 88100 Italy
Not yet recruiting
Arcispedale Santa Maria Nuova; Oncologia
Reggio Emilia Emilia-Romagna 42100 Italy
Not yet recruiting
Asst Papa Giovanni XXIII; Oncologia Medica
Bergamo Lombardia 24128 Italy
Not yet recruiting
Irccs Ospedale San Raffaele;Oncologia Medica
Milano Lombardia 20132 Italy
Not yet recruiting
Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda); Oncologico -Onc.Falck
Milano Lombardia 20162 Italy
Not yet recruiting
A.O. UNIVERSITARIA S. LUIGI GONZAGA; Oncologia Medica
Orbassano Piemonte 10043 Italy
Not yet recruiting
IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima
Padova Veneto 35128 Italy
Not yet recruiting
Seoul National University Hospital
Seoul 03080 Korea, Republic of
Not yet recruiting
Severance Hospital, Yonsei University Health System
Seoul 03722 Korea, Republic of
Not yet recruiting
Asan Medical Center
Seoul 05505 Korea, Republic of
Not yet recruiting
Samsung Medical Center
Seoul 6351 Korea, Republic of
Not yet recruiting
Riga East Clinical University Hospital Latvian Oncology Centre
Riga LV-1079 Latvia
Not yet recruiting
Sørlandet Sykehus Kristiansand
Kristiansand 4604 Norway
Not yet recruiting
Akershus universitetssykehus HF
Lørenskog 1478 Norway
Not yet recruiting
Oslo universitetssykehus HF, Ullevål, Kreftsenteret
Oslo 0450 Norway
Not yet recruiting
Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii
Krakow 31-531 Poland
Not yet recruiting
Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
Warszawa 02-781 Poland
Not yet recruiting
Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj Napoca; Oncologie Medicala
Cluj Napoca 400015 Romania
Not yet recruiting
Centrul de Oncologie Sfantul Nectarie
Craiova 200347 Romania
Not yet recruiting
Institutul Regional de Oncologie Iasi; Clinica de Hematologie
Iasi 700483 Romania
Not yet recruiting
Oncocenter Timisoara
Timişoara 300166 Romania
Not yet recruiting
Hospital Sant Joan Despi- Moises Broggi; Servicio de Oncologia
Sant Joan Despí Barcelona 08970 Spain
Not yet recruiting
Complejo Hospitalario de Navarra; Servicio de Oncologia
Pamplona Navarra 31008 Spain
Not yet recruiting
Hospital Clínic i Provincial; Servicio de Oncología
Barcelona 08036 Spain
Not yet recruiting
Institut Catala d Oncologia Hospital Duran i Reynals
Barcelona 08908 Spain
Not yet recruiting
Hospital Ramon y Cajal; Servicio de Oncologia
Madrid 28034 Spain
Not yet recruiting
Hospital Clinico San Carlos; Servicio de Oncologia
Madrid 28040 Spain
Not yet recruiting
Hospital Universitario 12 de Octubre; Servicio de Oncologia
Madrid 28041 Spain
Not yet recruiting
Hospital Quiron de Madrid; Servicio de Oncologia
Madrid 28223 Spain
Not yet recruiting
Hospital Universitario Virgen Macarena; Servicio de Oncologia
Sevilla 41009 Spain
Not yet recruiting
Hospital Universitari i Politecnic La Fe; Oncologia
Valencia 46026 Spain
Not yet recruiting
Universitaetsspital Basel; Onkologie
Basel 4031 Switzerland
Not yet recruiting
UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie
Zürich 8091 Switzerland
Not yet recruiting
Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology
Adana 01250 Turkey
Recruiting
Ankara University Medical Faculty; Medikal Onkoloji
Ankara 06100 Turkey
Recruiting
Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
Edirne 22030 Turkey
Recruiting
Istanbul University Cerrahpasa Medical Faculty; Medikal Onkoloji Departmani
Istanbul 34098 Turkey
Recruiting
Acıbadem Maslak Hastanesi Büyükdere
Sarıyer/İstanbul 34457 Turkey
Recruiting
Hacettepe Uni Medical Faculty Hospital; Oncology Dept
Sıhhiye, Ankara 06100 Turkey
Recruiting
Royal United Hospital; Oncology Department
Bath BA1 3NG United Kingdom
Not yet recruiting
Velindre Cancer Centre
Cardiff CF14 2TL United Kingdom
Not yet recruiting
Beatson West of Scotland Cancer Centre
Glasgow G12 0YN United Kingdom
Not yet recruiting
University College London Hospitals NHS Foundation Trust - University College Hospital
London NW1 2PG United Kingdom
Not yet recruiting
Hammersmith Hospital; Garry Weston Centre
London W12 0HS United Kingdom
Not yet recruiting
Christie Hospital NHS Trust
Manchester M20 4BX United Kingdom
Not yet recruiting
Freeman Hospital
Newcastle upon Tyne NE7 7DN United Kingdom
Not yet recruiting
Southampton General Hospital
Southampton SO16 6YD United Kingdom
Not yet recruiting

Location Countries

Country

Australia

Austria

Brazil

Bulgaria

Croatia

Czechia

Estonia

Finland

France

Germany

Greece

Hungary

Ireland

Italy

Korea, Republic of

Latvia

Norway

Poland

Romania

Spain

Switzerland

Turkey

United Kingdom



Verification Date

2018-07-01

Lastchanged Date

2018-05-03

Firstreceived Date

2018-04-05

Responsible Party

Responsible Party Type

Sponsor


Has Expanded Access

No

Condition Browse


Secondary Id

2017-003040-20

Number Of Arms

2

Intervention Browse

Mesh Term

Paclitaxel

Gemcitabine

Atezolizumab

Olaparib

Pertuzumab

Vemurafenib

Albumin-Bound Paclitaxel

Cisplatin

Bevacizumab

Carboplatin

Trastuzumab

Erlotinib Hydrochloride



Arm Group

Arm Group Label

Molecularly-Guided Therapy

Arm Group Type

Experimental

Description

Participants will be assigned molecularly-guided therapy based on genetic profile.


Arm Group Label

Platinum-Based Chemotherapy

Arm Group Type

Active Comparator

Description

Participants will receive platinum-doublet) chemotherapy (Carboplatin/Paclitaxel, Cisplatin/Gemcitabine, or Carboplatin/Gemcitabine)



Firstreceived Results Date

N/A

Acronym

CUPISCO

Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary Purpose

Treatment

Masking

None (Open Label)


Study First Submitted

April 5, 2018

Study First Submitted Qc

April 12, 2018

Study First Posted

April 13, 2018

Last Update Submitted

July 10, 2018

Last Update Submitted Qc

July 10, 2018

Last Update Posted

July 11, 2018


ClinicalTrials.gov processed this data on July 11, 2018

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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