Cancer of Unknown Primary SiteNorCUPNCT07366008
The NorCUP Trial: Improving Prognosis and Personalized Treatment in Cancer of Unknown Primary (CUP)
A study testing Comprehensive molecular profiling in people with Cancer of Unknown Primary Site, run by Haukeland University Hospital at 6 sites in Norway.
Trial summary
The goal of this clinical trial is to improve diagnosis and treatment strategies for patients with Cancer of Unknown Primary (CUP) by using advanced molecular profiling to identify the likely tumor origin and guide therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer of Unknown Primary Site
- What is being tested?
- Comprehensive molecular profiling
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 350 participants
- Where
- 6 sitesNorway
- Study dates
- Jan 2026to Jan 2033
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ECOG PS 0-2.
- Life expectancy minimum 3 months.
- Radiologically verified metastatic disease (CT thorax/abdomen/pelvis) with no radiological signs of primary tumor.
- Histologically verified metastatic disease of unknown primary. Morphological and immunohistochemical findings suggesting a possible, but not definitive, origo is eligible.
- Eligible histologies include adenocarcinoma, squamous cell carcinoma, poorly and undifferentiated carcinoma and undifferentiated neoplasms.
- Clinically relevant endoscopic examinations have been performed as indicated by clinical, radiological and pathological findings, without identification of a primary tumor.
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- Clinically relevant supplementary radiological examinations have been performed as indicated by clinical, radiological and pathological findings, with no radiological signs of primary tumor (e.g. PET/CT, mammography/MR mammae).
- Metastatic lesion available for biopsy. Protocol deviation may be allowed if lesion is not technically available for biopsy. For patients with metastatic lesion technically available for biopsy, the patient must be deemed medically fit to undergo a metastatic biopsy, as assessed by the investigator.
- Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Who cannot join
- Patients with any clinically significant medical or psychiatric condition which, in the opinion of the treating physician, makes it undesirable for the patient to participate in the study or which could jeopardize compliance with study requirements.
- Psychological, familial, sociological or geographical condition(s) potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
- Patient not able to give an informed consent or comply with study regulations as deemed by study investigator.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
Norway6 sites
Haukeland University Hospital
Bergen, 5021
Kjersti T Davidsen, MD PhD, 004755972010, kjersti.tefre.davidsen@helse-bergen.no
Akershus University Hospital
Oslo
Åsa D Smith, Asa.Dahle.Smith@ahus.no
Oslo University Hospital
Oslo
Elin Amdal, eliaam@ous-hf.no
Stavanger University Hospital
Stavanger
Bjørnar Gilje, bjornar.gilje@sus.no
University Hospital of North-Norway
Tromsø
Egil Blix, egil.store.blix@unn.no
St Olavs Hospital
Trondheim
Ola Magne Vagnildhaug, ola.magne.vagnildhaug@stolav.no
About this study
The goal of this clinical trial is to improve diagnosis and treatment strategies for patients with Cancer of Unknown Primary (CUP) by using advanced molecular profiling to identify the likely tumor origin and guide therapy.
The main questions it aims to answer are:
Read more
Can comprehensive molecular profiling help determine the origin of CUP tumors? Does identifying the tumor origin improve treatment choices and survival outcomes compared to historical data?
Participants will:
- Undergo a new biopsy to collect tumor tissue for advanced analyses.
- Provide blood samples for circulating tumor DNA (cfDNA/ctDNA) analyses.
- Provide a fecal sample for microbiome analysis.
- Have their tumor tissue analyzed using:
Methylation profiling and comprehensive gene panel testing.
- Have the results reviewed in a specialized CUP molecular MDT meeting to determine the likely tumor origin and guide treatment.
- Have their tumor tissue samples biobanked for further exploratory whole genome sequencing (WGS) and RNA sequencing.
- Conditions
- Cancer of Unknown Primary Site
- Being tested
- Comprehensive molecular profiling
- Keywords
- cancer of unknown primary site, neoplasms, unknown primary
- Medical subject headings
- Neoplasms, Unknown Primary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Comprehensive molecular profilingGenetic
Also called whole genome sequencing, RNA sequencing, Tumor methylation analyses, cfDNA methylation analyses
A fresh frozen biopsy and blood plasma for cfDNA analyses is taken upon inclusion for comprehensive molecular profiling. Results are discussed at a study specific CUP molecular MDT meeting.
| Study group | Role | What they receive |
|---|---|---|
| Comprehensive molecular profiling | Experimental | Tumor methylation analyses, cfDNA methylation analyses, Whole Genome Sequencing, RNA sequencing, Broad targeted NGS panel analyses Receives: Genetic: Comprehensive molecular profiling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients where the site of origin is identified
Site of origin identified is defined as the cases where the CUP molecular MDT concludes with a likely primary site of origin
Measured: From enrollment to the conclusion at the CUP molecular MDT at 8 weeks
Percentage of patients where treatment choice differs from empirical CUP regimen
Organ specific treatment chosen over empirical CUP treatment, based on the conclusion from the CUP MDT
Measured: From conclusion at the CUP molecular MDT to the start of subsequent treatment within a timeframe of 36 months from study inclusion
Secondary outcomes (5)
Progression free survival
The length of time from the start of treatment until disease progression or death from any cause, whichever occurs first.
Measured: From the date of first administration of a treatment line to the date of progression or death, or censored if alive at time of analysis, with a timeframe of 36 months from study inclusion.
Overall survival
Length of time from CUP diagnosis until death from any cause
Measured: From date of CUP diagnosis until death from any cause or censored if alive at date of analysis, within a timeframe of 36 months from study inclusion.
Identification of tumor site using molecular profiling methods
The percentage of patients in whom the likely site of origin is identified by each molecular profiling method.
Measured: From study enrollment to the conclusion at the CUP molecular MDT at 8 weeks
Incidence of molecular alterations and use of targeted treatment in CUP patients
The frequency of molecular alterations and actionable targets in patients with CUP, and the percentage of patients receiving targeted therapy based on molecular profiling results. The impact of targeted treatment on survival will also be evaluated.
Measured: From molecular profiling to initiation of targeted therapy and follow-up for survival outcomes, within a timeframe of 36 months from study inclusion.
Impact of CUP molecular MDT assessement on previous clinical work-up
This outcome evaluates the utility of CUP molecular MDT meetings by measuring the percentage of patients for whom additional clinical work-up or pathology analyses are recommended and the concordance between local and study pathologist conclusions.
Measured: From enrollment until CUP mol MDT at 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2026
- Study startJan 2026 (estimated)
- Primary completionJan 2033 (estimated)
- Study completionJan 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cancer of Unknown Primary SiteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Haukeland University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07366008
- Sponsor's protocol ID
- 869556
- Acronym
- NorCUP
- Status last verified
- Dec 2025
- First submitted
- 19 Dec 2025
- Last updated
- 26 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No