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NCT Number: NCT07366008

The NorCUP Trial: Improving Prognosis and Personalized Treatment in Cancer of Unknown Primary (CUP)

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:

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.

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Key information

Conditions

Cancer of Unknown Primary Site Neoplasm Metastasis Neoplasms Neoplasms, Unknown Primary Neoplastic Processes Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Haukeland University Hospital, Bergen, Norway

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.
  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

Comprehensive molecular profiling

Genetic

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.

Other names: whole genome sequencing, RNA sequencing, Tumor methylation analyses, cfDNA methylation analyses, Broad targeted NGS panel

Primary outcomes

  1. Percentage of patients where the site of origin is identified

    Time frame: From enrollment to the conclusion at the CUP molecular MDT at 8 weeks

    Site of origin identified is defined as the cases where the CUP molecular MDT concludes with a likely primary site of origin

  2. Percentage of patients where treatment choice differs from empirical CUP regimen

    Time frame: From conclusion at the CUP molecular MDT to the start of subsequent treatment within a timeframe of 36 months from study inclusion

    Organ specific treatment chosen over empirical CUP treatment, based on the conclusion from the CUP MDT

Secondary outcomes

  1. Progression free survival

    Time frame: 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.

    The length of time from the start of treatment until disease progression or death from any cause, whichever occurs first.

  2. Overall survival

    Time frame: 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.

    Length of time from CUP diagnosis until death from any cause

  3. Identification of tumor site using molecular profiling methods

    Time frame: From study enrollment to the conclusion at the CUP molecular MDT at 8 weeks

    The percentage of patients in whom the likely site of origin is identified by each molecular profiling method.

  4. Incidence of molecular alterations and use of targeted treatment in CUP patients

    Time frame: From molecular profiling to initiation of targeted therapy and follow-up for survival outcomes, within a timeframe of 36 months from study inclusion.

    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.

  5. Impact of CUP molecular MDT assessement on previous clinical work-up

    Time frame: From enrollment until CUP mol MDT at 8 weeks

    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.

Other outcomes

  1. Fecal Microbiome Diversity and Composition in CUP Patient

    Time frame: From baseline stool sample collection through completion of analyses within a timeframe of 36 months from study inclusion

    Characterization of the fecal microbiome in patients with cancer of unknown primary (CUP)

Study contacts

Contact information is provided by the study sponsor or research team.

Eli Sihn S Steinskog, MD PhD

CONTACT

[email protected]

0047

Sponsors and collaborators

Lead sponsor

Haukeland University Hospital

Other

Registry information

Acronym: NorCUP

Important dates

Study start
2026
Primary completion
2033
Study completion
2033
First posted
Jan 26, 2026
Registry last updated
Jan 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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