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

NCT07366008 | Not Yet Recruiting DMC

• 1 other identifier: 869556
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 6

Brief 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. 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.

Conditions

Cancer of Unknown Primary Site

Keywords

cancer of unknown primary site; neoplasms, unknown primary

Outcome Measures

Primary Outcomes (2)

• 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

  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

  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

  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

  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

  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

  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

  From enrollment until CUP mol MDT at 8 weeks

Other Outcomes (1)

• Fecal Microbiome Diversity and Composition in CUP Patient

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

Study Arms (1)

Comprehensive molecular profiling

EXPERIMENTAL

Tumor methylation analyses, cfDNA methylation analyses, Whole Genome Sequencing, RNA sequencing, Broad targeted NGS panel analyses

Genetic: Comprehensive molecular profiling

Interventions

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.

Also known as: whole genome sequencing, RNA sequencing, Tumor methylation analyses, cfDNA methylation analyses, Broad targeted NGS panel

Comprehensive molecular profiling

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Haukeland University Hospital: lead

Study Sites (6)

Haukeland University Hospital

Bergen, 5021, Norway

Location

Akershus University Hospital

Oslo, Norway

Location

Oslo University Hospital

Oslo, Norway

Location

Stavanger University Hospital

Stavanger, Norway

Location

University Hospital of North-Norway

Tromsø, Norway

Location

St Olavs Hospital

Trondheim, Norway

Location

MeSH Terms

Conditions

Neoplasms, Unknown Primary

Interventions

Whole Genome Sequencing; Sequence Analysis, RNA

Condition Hierarchy (Ancestors)

Neoplasm Metastasis; Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques

Central Study Contacts

Eli Sihn S Steinskog, MD PhD

CONTACT

0047; eli.sihn.samdal.steinskog@helse-bergen.no

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2025
• First Posted: January 26, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2033
• Study Completion (Estimated): January 1, 2033
• Last Updated: January 26, 2026

Record last verified: 2025-12

Locations

NO (6)