Use the search to find what you are looking for



The list of trials by country that we know about are shown below with an explanation. We are always grateful for information and updates about trials from scientists and clinicians:

European Union

Register of all clinical trials


Agnostos Precision Medicine Project

The AGNOSTOS project represents a unique clinical and translational initiative that aims to improve the outlook of patients with CUP through evaluation of novel chemotherapeutic regimens (AGNOSTOS TRIAL) and a better comprehension of biology behind this complex entity (AGNOSTOS TRASLATIONAL COMPANION STUDY).

AGNOSTOS TRIAL is a multicentric phase 2 randomized trial with a ‘pick-the-winner design’ in chemo-naive patients with cancer of unknown primary. It will assess the efficacy of the two best active single agent – carboplatin or gemcitabine – added to an innovative taxane back bone (nab-Paclitaxel).
Primary objective is to assess efficacy (as measured as tumor response) of nab-paclitaxel in combination with either carboplatin or gemcitabine while secondary objectives are evaluation of duration of response, time to progression and overall survival of CUP patients after nab-paclitaxel-gemcitabine or nab-paclitaxel-carboplatin. Patients can withdraw from the trial at any time without giving a reason. The trial may help in the future with selecting the best chemotherapy for patients with CUP.

AGNOSTOS TRASLATIONAL COMPANION STUDY will deploy the extensive genomic work-up of enrolled patients to pinpoint common denominators of the hypermetastatic phenotype and it will exploit patient-derived-xenograft for an in-depth molecular characterization of these tumors, with the potential to unravel the molecular link between cancer stemness and the hypermetastatic phenotype.

If you need help to find the contact details of a particular centre involved with the trial you can contact Dr. Filippo Montemurro or Dr. Elena GEUNA
Istituto di Candiolo, Fondazione Piemonte Oncologia (FPO), IRCCS, Italy
Telephone: +39 0119933250.

Useful link:




Studying the biology of Cancer of Unknown Primary (CUP).   Most CUP clinical research now involves “translational” aspects, in the expectation that greater understanding of underlying biological factors can  be exploited to develop more rational treatments. Such studies may  involve analysing CUP tumours at the molecular level, and comparing them with better understood cancers. Translational studies also aim to correlate outcomes of treatment with underlying biological features to assist in selection of therapy for future patients.   Dr George Pentheroudakis and Prof Nicholas Pavlidis from the School of Medicine of the University of Ioannina (Greece) have been pursing this course, and have a broad translational programme which is investigating the following:  Factors which may explain the highly metastatic behaviour of some CUP tumours (examining the presence of Epithelial Mesenchymal Transition (EMT) transcriptional activity at the invasive front and at the centre of CUP metastatic deposits, and by studying the presence of circulating tumour cells in the blood of CUP patients) Factors which may explain the aggressive behaviour of some CUP tumours (examining the activity of multiple cellular signalling pathways in CUP metastatic deposits by means of reverse phase microarray-based phosphoproteomic profiling.) Understanding of these pathways may offer opportunities for rationally selected targeted therapy using existing or novel drugs. The correlation between chemotherapy drug handling in individuals treated for CUP, and their response to therapy (by the pharmacogenomic analysis of cellular enzymes in CUP metastases). The correlation between various clinical features (epidemiology, presentation, treatment) and the outcome for patients with distinct clinicopathologic CUP subsets. This may allow more “tailored” treatment in future using existing drug options.


France and Northern Europe

GEFCAPI 04 (a la carte)

ThisPhase III trial is due to begin in France in 2010 under the auspices of the Groupe d’Etude des Carcinomes de Primitifs Inconnus (GEFCAPI) with the co-operation of investigators from the Netherlands, Denmark, and Sweden..

The study is a phase III randomized trial with the aim of demonstrating the superiority of a molecular analysis-oriented treatment versus empiric chemotherapy in patients with CUP. After accrual, patients will be randomized to receive:   – either the Cisplatin-Gemcitabine regimen (arm A)   – or a treatment considered as standard at the time of patient inclusion based on the primary cancer suspected by the Pathwork Tissue Of Origin® Test, which may consist in a chemotherapy regimen and/or a so-called targeted therapy (arm B).       France   BelCaP in CUP   Sponsor: TopoTarget A/S   Started Mar 2009   To provide an estimate of the hazard ratio of treatment effect when the combination of belinostat plus carboplatin and paclitaxel (BelCaP) is compared with the combination of carboplatin and paclitaxel in terms of progression-free survival for patients with carcinoma of unknown primary site.       Germany   PACET-CUP   Sponsor: Ruprecht-Karls-University of Heidelberg   Started Dec 2008   Open-labeled, randomized multi-center phase II study evaluating the efficacy and safety of Paclitaxel/ Carboplatin with and without Cetuximab as first-line treatment of adeno- and undifferentiated carcinoma of unknown primary (CUP).



UNKPRI 20 and UNKPRI 21 – Currently in progress with Dr Greco and colleagues at The Sarah Cannon Cancer Center, USA.

UNKPRI 20  is a Phase II Study of Chemotherapy Treatment Based on Molecular Profiling Diagnosis for Patients with Carcinoma of Unknown Primary Site.  This study is prospectively evaluating molecular profile predictions of the primary site to use site directed therapy. They hope to show improved outcomes compared to the expected historic outcomes with empiric treatment in several subsets of patients.

UNKPRI 21  is an open-label randomized Phase II trial of Belinostat (PXD101) in combination with Carboplatin and Paclitaxel (BelCAP) compared to Carboplatin and Paclitaxel in patients with previously untreated carcinoma of unknown primary site. This study uses standard empiric treatment compared to the same plus the HDAC inhibitor Belinostat. HDAC inhibitors have been found to be useful in selected cancers and this study may lead to a Phase III trial depending on the results.

[Note: Histone deacetylases (HDAC) is a family of enzymes that may act as master regulators of many diseases, including cancer, because they are involved in the control of gene expression. HDAC inhibitors selectively switch on tumour suppressor genes, something traditional chemotherapy may not do.]


There is a listing of trials in the USA related to the treatment of CUP patients here:



SUPER – Solving Unknown Primary cancER.

Sponsor: Peter MacCallum Cancer Centre, Melbourne, Australia.

This is a prospective cohort study to create a national information resource and improve the understanding of the molecular biology, clinical, quality of life and psychosocial characteristics of patients with Cancer of Unknown Primary (CUP). The study will be running from 2013-2016 and will recruit 220 patients from metropolitan and regional sites across Australia. Research seeking access to the samples collected as part of this study will look to determine the frequency of clinically actionable mutations in CUP tumour samples and evaluate the impact of performing molecular diagnostic tests and feedback of results to influence clinical care of CUP patients. The project will also seek to establish reliable estimates for quality of life and psychosocial needs across the CUP illness trajectory and to identify similarities and differences between CUP and non-CUP patients from baseline to 12-month follow-up. The long-term objectives of this project are to: significantly improve the diagnostic assessment of CUP patients, integrate new treatment approaches based on molecular therapeutics and likely site of origin, and develop tailored supportive care intervention programs for patients with CUP.



Cost-effectiveness Study of miRview™ Mets in Patients With Cancer of Unknown Primary (CUP) by Teva Pharmaceutical Industries with Rosetta Genomics and Clalit Health Services in Israel running from May 2010 – April 2012.

The purpose was to compare the cost-effectiveness of miRview™ mets test with conventional work-up in cancer of unknown primary (CUP) patients, by comparing total cost and time of the diagnostic process (including hospitalization time) from day 1 of the study to the decision on treatment program

Patients of group 1 will be submitted to the standard conventional work-up as well as miRview™ mets assay. Their physician will treat the patient based upon both results. Patients of group 2 will be submitted to the standard conventional work-up. miRview™ mets assay will be performed but will remain blinded for both the patient and referring physician. Treatment will be decided based on standard work-up results.



All UK clinical trials

CUP-One.  Trial closed end 2014.  For an overview of the trial and eligibility details click here.  It has been extended to 2014. The trial is not suitable for all CUP patients and if you are interested you should discuss it with your oncologist. Note that the biopsy sample will need to be “generous” i.e. from a core or incisional biopsy.

If you need help to find the contact details of a particular centre involved with the trial you can contact Lynn McMahon, Project Manager, Cancer Research UK Clinical Trials Unit. Telephone:  0141 301 7194 (++ 44 141 301 7194). eMail: .

CUP-One is a multi-centre, Phase II, trial sponsored by the Greater Glasgow Health Board/University of Glasgow, funded by NCRI/CRUK and co-ordinated by the CRUK Clinical Trials Unit in Glasgow. There are more details here.

The study is in two parts: the aim of the first (translational) part is to prospectively validate new tools in diagnosis (including molecular profiling, metabonomics of blood and urine for response and toxicity prediction and a proposed immunohistochemistry classifier). The hope is that, in the future, scientists can find a diagnostic indicator of the primary site simply, rather than trying a whole barrage of investigations.

Patients in whom a primary site is not identified can then be entered into the second (clinical) part of the trial. This part aims to establish the efficacy of the ECX chemo regimen (ECX stands for the drugs: Epirubicin, Cisplatin and Capecitabine) with and without Vandetanib (an inhibitor of different intracellular signaling pathways involved in tumour growth, progression, and angiogenesis). The treatment will last initially for 3 months and there will be subsequent monitoring. Patients can withdraw from the trial at any time without giving a reason. The trial may help in the future with selecting the best chemotherapy for patients with CUP.

Overall, this study should allow a more logical framework to be derived, both clinically and biologically, as to how highly metastatic cancers may be efficiently and economically investigated and managed in the future. It will be some years before the findings are available from this trial.

Useful links:

For general information about trials see