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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03498521




Registration number
NCT03498521
Ethics application status
Date submitted
5/04/2018
Date registered
13/04/2018
Date last updated
18/11/2023

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2017-003040-20
Secondary ID [2] 0 0
MX39795
Universal Trial Number (UTN)
Trial acronym
CUPISCO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer of Unknown Primary Site 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Alectinib
Treatment: Drugs - Vismodegib
Treatment: Drugs - Ipatasertib
Treatment: Drugs - Olaparib
Treatment: Drugs - Erlotinib
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Vemurafenib
Treatment: Drugs - Cobimetinib
Treatment: Drugs - Trastuzumab Subcutaneous (SC)
Treatment: Drugs - Pertuzumab
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Carboplatin
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Cisplatin
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Entrectinib
Treatment: Drugs - Ivosidenib
Treatment: Drugs - Pemigatinib

Experimental: Molecularly-Guided Therapy - Participants will be assigned to molecularly-guided therapy based on genomic profile.

Active Comparator: Platinum-Based Chemotherapy - Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel).


Treatment: Drugs: Alectinib
Alectinib will be administered orally at the label-recommended dose (600 mg) twice daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).

Treatment: Drugs: Vismodegib
Vismodegib will be administered orally at the label-recommended dose (150 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).

Treatment: Drugs: Ipatasertib
Ipatasertib will be administered orally at the label-recommended dose (400 mg) once daily on Days 1-21 of each 28-day Cycle in combination with paclitaxel, and as monotherapy after the final administration of paclitaxel, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).

Treatment: Drugs: Olaparib
Olaparib will be administered orally at the label-recommended dose (400 mg) twice daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).

Treatment: Drugs: Erlotinib
Erlotinib will be administered orally in combination with Bevacizumab at the label recommended dose (150 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)

Treatment: Drugs: Bevacizumab
Bevacizumab will be administered intravenously at 15mg/kg every 3 weeks in combination with Erlotinib until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)

Treatment: Drugs: Vemurafenib
Vemurafenib will be administered orally, 960 mg twice daily, in combination with Cobimetinib, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)

Treatment: Drugs: Cobimetinib
Cobimetinib will be administered orally, 60mg once daily, in combination with Vemurafenib, on Days 1-21 of each 28-day Cycle, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)

Treatment: Drugs: Trastuzumab Subcutaneous (SC)
Trastuzumab will be administered subcutaneously, 600 mg every 3 weeks, in combination with Pertuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)

Treatment: Drugs: Pertuzumab
Pertuzumab will be initially be administered intravenously, 840 mg, followed by 420 mg every 3 weeks, in combination with Trastuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)

Treatment: Drugs: Atezolizumab
Atezolizumab will be administered intravenously at the label-recommended dose (1200 mg), alone or in combination with chemotherapy, every 3 weeks until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).

Treatment: Drugs: Carboplatin
Carboplatin will be administered intravenously at the area under the curve (AUC) dose once every 3 weeks for up to 9 Cycles (Cycle = 21 days) in some combination with the following: Paclitaxel, Gemcitabine, Atezolizumab, Pertuzumab, and Trastuzumab SC.

Treatment: Drugs: Paclitaxel
Paclitaxel will be administered intravenously, 175 mg/m^2, once every 3 weeks for up to 9 cycles (Cycle = 21 days) in some combination with the following: Carboplatin, Ipatasertib, Atezolizumab, Pertuzumab, and Trastuzumab SC

Treatment: Drugs: Cisplatin
Cisplatin will be administered intravenously, 60-75 mg/m^2, once every three weeks, for up to 9 cycles (Cycle = 21 days) in some combination with the following: Gemcitabine, Paclitaxel, Atezolizumab, Pertuzumab, and Trastuzumab SC.

Treatment: Drugs: Gemcitabine
Gemcitabine will be administered intravenously, 1000 mg/m^2, twice every three weeks for up to 9 cycles (Cycle = 21 days) in some combination with the following: Cisplatin, Carboplatin, Atezolizumab, Pertuzumab, and Trastuzumab SC.

Treatment: Drugs: Entrectinib
Entrectinib will be administered orally at the label-recommended dose (600 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).

Treatment: Drugs: Ivosidenib
Ivosidenib will be administered orally at the label-recommended dose (500mg) once daily across a 28-day treatment cycle until loss of clinical benefit or unacceptable toxicity.

Treatment: Drugs: Pemigatinib
Pemigatinib will be administered orally at the label-recommended dose (13.5mg) once daily across a 21-day treatment cycle until loss of clinical benefit or unacceptable toxicity.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS1)
Timepoint [1] 0 0
From 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 70 months)
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From randomization to death from any cause, through the end of study (approximately 70 months)
Secondary outcome [2] 0 0
Objective Response Rate (ORR1)
Timepoint [2] 0 0
Two consecutive occurrences of complete or partial response >/=4 weeks apart
Secondary outcome [3] 0 0
Duration of Response (DOR1)
Timepoint [3] 0 0
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 70 months)
Secondary outcome [4] 0 0
Disease Control Rate (DCR1)
Timepoint [4] 0 0
From randomization to death from any cause, through the end of study (approximately 70 months)
Secondary outcome [5] 0 0
Percentage of Participants with Adverse Events (AEs)
Timepoint [5] 0 0
From baseline through the end of study (approximately 70 months)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/07/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
9/06/2024
Actual
Sample size
Target
790
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [2] 0 0
Northern Cancer Institute - St Leonards
Recruitment hospital [3] 0 0
Icon Cancer Foundation - South Brisbane
Recruitment hospital [4] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [5] 0 0
Peter MacCallum Cancer Center - North Melbourne
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
5042 - Bedford Park
Recruitment postcode(s) [5] 0 0
3051 - North Melbourne
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Graz
Country [2] 0 0
Austria
State/province [2] 0 0
Salzburg
Country [3] 0 0
Austria
State/province [3] 0 0
Wien
Country [4] 0 0
Brazil
State/province [4] 0 0
BA
Country [5] 0 0
Brazil
State/province [5] 0 0
RJ
Country [6] 0 0
Brazil
State/province [6] 0 0
RS
Country [7] 0 0
Brazil
State/province [7] 0 0
SP
Country [8] 0 0
Bulgaria
State/province [8] 0 0
Sofia
Country [9] 0 0
Chile
State/province [9] 0 0
Recoleta
Country [10] 0 0
Chile
State/province [10] 0 0
Temuco
Country [11] 0 0
Colombia
State/province [11] 0 0
Bogota
Country [12] 0 0
Colombia
State/province [12] 0 0
Monteria
Country [13] 0 0
Croatia
State/province [13] 0 0
Zagreb
Country [14] 0 0
Czechia
State/province [14] 0 0
Brno
Country [15] 0 0
Czechia
State/province [15] 0 0
Olomouc
Country [16] 0 0
Czechia
State/province [16] 0 0
Praha 2
Country [17] 0 0
Denmark
State/province [17] 0 0
Aarhus N
Country [18] 0 0
Denmark
State/province [18] 0 0
København Ø
Country [19] 0 0
Estonia
State/province [19] 0 0
Tallinn
Country [20] 0 0
Finland
State/province [20] 0 0
Helsinki
Country [21] 0 0
Finland
State/province [21] 0 0
Tampere
Country [22] 0 0
France
State/province [22] 0 0
Angers
Country [23] 0 0
France
State/province [23] 0 0
Besançon
Country [24] 0 0
France
State/province [24] 0 0
Bordeaux
Country [25] 0 0
France
State/province [25] 0 0
Caen
Country [26] 0 0
France
State/province [26] 0 0
Clermont-ferrand
Country [27] 0 0
France
State/province [27] 0 0
Lyon
Country [28] 0 0
France
State/province [28] 0 0
Marseille Cedex 09
Country [29] 0 0
France
State/province [29] 0 0
Montpellier
Country [30] 0 0
France
State/province [30] 0 0
Nice
Country [31] 0 0
France
State/province [31] 0 0
Paris
Country [32] 0 0
France
State/province [32] 0 0
Pierre-Benite (Lyon)
Country [33] 0 0
France
State/province [33] 0 0
Rennes
Country [34] 0 0
France
State/province [34] 0 0
Strasbourg
Country [35] 0 0
France
State/province [35] 0 0
Suresnes
Country [36] 0 0
France
State/province [36] 0 0
Villejuif
Country [37] 0 0
Germany
State/province [37] 0 0
Augsburg
Country [38] 0 0
Germany
State/province [38] 0 0
Berlin
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Germany
State/province [39] 0 0
Dachau
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Germany
State/province [40] 0 0
Dresden
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Germany
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Düsseldorf
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Germany
State/province [42] 0 0
Essen
Country [43] 0 0
Germany
State/province [43] 0 0
Frankfurt
Country [44] 0 0
Germany
State/province [44] 0 0
Heidelberg
Country [45] 0 0
Germany
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Heilbronn
Country [46] 0 0
Germany
State/province [46] 0 0
Jena
Country [47] 0 0
Germany
State/province [47] 0 0
Mainz
Country [48] 0 0
Germany
State/province [48] 0 0
Mannheim
Country [49] 0 0
Germany
State/province [49] 0 0
München
Country [50] 0 0
Germany
State/province [50] 0 0
Münster
Country [51] 0 0
Germany
State/province [51] 0 0
Oldenburg / Holstein
Country [52] 0 0
Greece
State/province [52] 0 0
Athens
Country [53] 0 0
Greece
State/province [53] 0 0
Heraklion
Country [54] 0 0
Greece
State/province [54] 0 0
Ioannina
Country [55] 0 0
Greece
State/province [55] 0 0
Thessaloniki
Country [56] 0 0
Hungary
State/province [56] 0 0
Budapest
Country [57] 0 0
Hungary
State/province [57] 0 0
Kecskemét
Country [58] 0 0
Ireland
State/province [58] 0 0
Dublin
Country [59] 0 0
Ireland
State/province [59] 0 0
Waterford
Country [60] 0 0
Israel
State/province [60] 0 0
Petach Tikva
Country [61] 0 0
Israel
State/province [61] 0 0
Ramat Gan
Country [62] 0 0
Israel
State/province [62] 0 0
Tel Aviv
Country [63] 0 0
Italy
State/province [63] 0 0
Basilicata
Country [64] 0 0
Italy
State/province [64] 0 0
Calabria
Country [65] 0 0
Italy
State/province [65] 0 0
Campania
Country [66] 0 0
Italy
State/province [66] 0 0
Emilia-Romagna
Country [67] 0 0
Italy
State/province [67] 0 0
Lombardia
Country [68] 0 0
Italy
State/province [68] 0 0
Veneto
Country [69] 0 0
Japan
State/province [69] 0 0
Aichi
Country [70] 0 0
Japan
State/province [70] 0 0
Chiba
Country [71] 0 0
Japan
State/province [71] 0 0
Fukuoka
Country [72] 0 0
Korea, Republic of
State/province [72] 0 0
Seoul
Country [73] 0 0
Latvia
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Riga
Country [74] 0 0
Mexico
State/province [74] 0 0
Mexico CITY (federal District)
Country [75] 0 0
Mexico
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Nuevo LEON
Country [76] 0 0
Netherlands
State/province [76] 0 0
Rotterdam
Country [77] 0 0
Netherlands
State/province [77] 0 0
Utrecht
Country [78] 0 0
Netherlands
State/province [78] 0 0
Venlo
Country [79] 0 0
Norway
State/province [79] 0 0
Kristiansand
Country [80] 0 0
Norway
State/province [80] 0 0
Lørenskog
Country [81] 0 0
Norway
State/province [81] 0 0
Oslo
Country [82] 0 0
Peru
State/province [82] 0 0
Lima
Country [83] 0 0
Poland
State/province [83] 0 0
Kraków
Country [84] 0 0
Poland
State/province [84] 0 0
Warszawa
Country [85] 0 0
Portugal
State/province [85] 0 0
Porto
Country [86] 0 0
Romania
State/province [86] 0 0
Cluj Napoca
Country [87] 0 0
Romania
State/province [87] 0 0
Craiova
Country [88] 0 0
Romania
State/province [88] 0 0
Iasi
Country [89] 0 0
Romania
State/province [89] 0 0
Timi?oara
Country [90] 0 0
Spain
State/province [90] 0 0
Barcelona
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Spain
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Navarra
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Spain
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Pontevedra
Country [93] 0 0
Spain
State/province [93] 0 0
Madrid
Country [94] 0 0
Spain
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Malaga
Country [95] 0 0
Spain
State/province [95] 0 0
Sevilla
Country [96] 0 0
Spain
State/province [96] 0 0
Valencia
Country [97] 0 0
Spain
State/province [97] 0 0
Zaragoza
Country [98] 0 0
Switzerland
State/province [98] 0 0
Basel
Country [99] 0 0
Switzerland
State/province [99] 0 0
Zürich
Country [100] 0 0
Thailand
State/province [100] 0 0
Bangkok
Country [101] 0 0
Turkey
State/province [101] 0 0
Adana
Country [102] 0 0
Turkey
State/province [102] 0 0
Ankara
Country [103] 0 0
Turkey
State/province [103] 0 0
Antalya
Country [104] 0 0
Turkey
State/province [104] 0 0
Edirne
Country [105] 0 0
Turkey
State/province [105] 0 0
Istanbul
Country [106] 0 0
Turkey
State/province [106] 0 0
Kar?iyaka
Country [107] 0 0
Turkey
State/province [107] 0 0
Sihhiye/Ankara
Country [108] 0 0
United Kingdom
State/province [108] 0 0
Bath
Country [109] 0 0
United Kingdom
State/province [109] 0 0
Cardiff
Country [110] 0 0
United Kingdom
State/province [110] 0 0
Edinburgh
Country [111] 0 0
United Kingdom
State/province [111] 0 0
Glasgow
Country [112] 0 0
United Kingdom
State/province [112] 0 0
London
Country [113] 0 0
United Kingdom
State/province [113] 0 0
Manchester
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Newcastle upon Tyne
Country [115] 0 0
United Kingdom
State/province [115] 0 0
Southampton
Country [116] 0 0
United Kingdom
State/province [116] 0 0
Torquay

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Foundation Medicine, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03498521
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03498521