AzTrials
AzTrials

Unknown Primary TumorsNCT06140992

PaCIFiC-CUP Classifies Cancer of Unknown Primary

An observational study of Unknown Primary Tumors and DNA Methylation, run by Sun Yat-sen University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This study aims to initially utilize machine learning on pan-cancer DNA methylation data from public databases to construct a DNA methylation classification model (PaCIFiC-CUP, pan-cancer integrated fingerprinting classifier of CUP) for diagnosing various types of cancer, particularly the primary site of cancer of… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Unknown Primary Tumors, DNA Methylation
How many people
120 participants
Where
1 siteChina
Study dates
1 Jul 2023to 31 Dec 2026
Phase
Observational
Are there results?
Not yet: the study is under way

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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: The study population consists of patients diagnosed with CUP who meet the inclusion and exclusion criteria.

Who may be able to join

  • The patient specimens were obtained from the Sun Yat-sen University Cancer Center and affiliated cooperating centers, with written consent from the patients authorizing the use of the specimens for research purposes.
  • Following standard assessments (medical history, physical examination, complete blood count, biochemistry, computed tomography scans of the neck, chest, abdomen, and pelvis, targeted evaluations of all symptomatic areas, pathology, and immunohistochemistry), the diagnosis was determined as a primary site unknown tumor (including adenocarcinoma, squamous cell carcinoma, undifferentiated carcinoma, neuroendocrine carcinoma, sarcoma, etc).
  • The diagnosis was confirmed at the participating institution and the patient had received systemic therapy.
  • Complete clinical, pathological, and follow-up data for the patients can be obtained.
  • ECOG performance status score: 0-2 points.

Who cannot join

  • Pregnant or lactating female patients.
  • Tumor tissue sample size is too small (tumor tissue accounts for <70% in the biopsy or slice tissue).
  • Organ transplant or history of non-autologous (allogeneic) bone marrow or stem cell transplantation.
  • History of previous tumors, with the current condition being a recurrent tumor.
  • Hematological malignancies (excluding lymphoma).
  • Other diseases that may severely impact patient survival, such as severe cardiovascular or cerebrovascular diseases, sepsis, severe trauma or burns, etc.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Yiyang Zhang contact

+8615652797092

zhangyy@sysucc.org.cn

China1 site, 1 recruiting

  • Sun Yat-sen university cancer center

    Guangzhou, Guangdong, 510060

    Yiyang Zhang, +8615652797092, zhangyy@sysucc.org.cn

    Recruiting

Other trials in China

About this study

Official title: PaCIFiC-CUP：Pan-Cancer Integrated Fingerprinting Classifier for Identifying the Origin of Cancer of Unknown Primary: A Multi-Center Prospective Cohort Study

This study aims to initially utilize machine learning on pan-cancer DNA methylation data from public databases to construct a DNA methylation classification model (PaCIFiC-CUP, pan-cancer integrated fingerprinting classifier of CUP) for diagnosing various types of cancer, particularly the primary site of cancer of unknown primary. The goal is to achieve diagnosis of cancer pathology type by analyzing the DNA methylation patterns of cancer specimens, thereby guiding subsequent precision treatment for cancer.

Keywords
Unknown Primary Tumors, DNA methylation, Large Language Model, Pan-cancer
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.

Study groups in NCT06140992
Study groupRoleWhat they receive
Site-Specific Therapy GroupThese patients with cancer of unknown primary received site-specific therapy that matched the particular site predicted by the DNA methylation classifier.
Empirical Therapy GroupThese patients with cancer of unknown primary received empirical therapy that didn't match the particular site predicted by the DNA methylation classifier.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival

    Overall survival refers to the length of time that a person lives after being diagnosed with cancer of unknown primary, without regard to any specific cause of death.

    Measured: From date of diagnosis until the date of death from any cause, assessed up to 24 months

Secondary outcomes (1)

  1. Progression-Free Survival

    Progression-Free Survival refers to the length of time during which a patient with cancer of unknown primary remains alive without any signs or symptoms of disease progression

    Measured: From date of diagnosis until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Nov 2023
  2. Study start1 Jul 2023
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06140992
Sponsor's protocol ID
PaCIFiC-CUP
Status last verified
Apr 2026
First submitted
14 Nov 2023
Last updated
23 Apr 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Kramer A, Bochtler T, Pauli C, Baciarello G, Delorme S, Hemminki K, Mileshkin L, Moch H, Oien K, Olivier T, Patrikidou A, Wasan H, Zarkavelis G, Pentheroudakis G, Fizazi K; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023 Mar;34(3):228-246. doi: 10.1016/j.annonc.2022.11.013. Epub 2022 Dec 20. No abstract available.

    PubMed 36563965

  • Paziewska A, Dabrowska M, Goryca K, Antoniewicz A, Dobruch J, Mikula M, Jarosz D, Zapala L, Borowka A, Ostrowski J. DNA methylation status is more reliable than gene expression at detecting cancer in prostate biopsy. Br J Cancer. 2014 Aug 12;111(4):781-9. doi: 10.1038/bjc.2014.337. Epub 2014 Jun 17.

    PubMed 24937670

  • Wehmas LC, Hester SD, Wood CE. Direct formalin fixation induces widespread transcriptomic effects in archival tissue samples. Sci Rep. 2020 Sep 2;10(1):14497. doi: 10.1038/s41598-020-71521-w.

    PubMed 32879405

  • Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D, Koelsche C, Sahm F, Chavez L, Reuss DE, Kratz A, Wefers AK, Huang K, Pajtler KW, Schweizer L, Stichel D, Olar A, Engel NW, Lindenberg K, Harter PN, Braczynski AK, Plate KH, Dohmen H, Garvalov BK, Coras R, Holsken A, Hewer E, Bewerunge-Hudler M, Schick M, Fischer R, Beschorner R, Schittenhelm J, Staszewski O, Wani K, Varlet P, Pages M, Temming P, Lohmann D, Selt F, Witt H, Milde T, Witt O, Aronica E, Giangaspero F, Rushing E, Scheurlen W, Geisenberger C, Rodriguez FJ, Becker A, Preusser M, Haberler C, Bjerkvig R, Cryan J, Farrell M, Deckert M, Hench J, Frank S, Serrano J, Kannan K, Tsirigos A, Bruck W, Hofer S, Brehmer S, Seiz-Rosenhagen M, Hanggi D, Hans V, Rozsnoki S, Hansford JR, Kohlhof P, Kristensen BW, Lechner M, Lopes B, Mawrin C, Ketter R, Kulozik A, Khatib Z, Heppner F, Koch A, Jouvet A, Keohane C, Muhleisen H, Mueller W, Pohl U, Prinz M, Benner A, Zapatka M, Gottardo NG, Driever PH, Kramm CM, Muller HL, Rutkowski S, von Hoff K, Fruhwald MC, Gnekow A, Fleischhack G, Tippelt S, Calaminus G, Monoranu CM, Perry A, Jones C, Jacques TS, Radlwimmer B, Gessi M, Pietsch T, Schramm J, Schackert G, Westphal M, Reifenberger G, Wesseling P, Weller M, Collins VP, Blumcke I, Bendszus M, Debus J, Huang A, Jabado N, Northcott PA, Paulus W, Gajjar A, Robinson GW, Taylor MD, Jaunmuktane Z, Ryzhova M, Platten M, Unterberg A, Wick W, Karajannis MA, Mittelbronn M, Acker T, Hartmann C, Aldape K, Schuller U, Buslei R, Lichter P, Kool M, Herold-Mende C, Ellison DW, Hasselblatt M, Snuderl M, Brandner S, Korshunov A, von Deimling A, Pfister SM. DNA methylation-based classification of central nervous system tumours. Nature. 2018 Mar 22;555(7697):469-474. doi: 10.1038/nature26000. Epub 2018 Mar 14.

    PubMed 29539639

  • Koelsche C, Schrimpf D, Stichel D, Sill M, Sahm F, Reuss DE, Blattner M, Worst B, Heilig CE, Beck K, Horak P, Kreutzfeldt S, Paff E, Stark S, Johann P, Selt F, Ecker J, Sturm D, Pajtler KW, Reinhardt A, Wefers AK, Sievers P, Ebrahimi A, Suwala A, Fernandez-Klett F, Casalini B, Korshunov A, Hovestadt V, Kommoss FKF, Kriegsmann M, Schick M, Bewerunge-Hudler M, Milde T, Witt O, Kulozik AE, Kool M, Romero-Perez L, Grunewald TGP, Kirchner T, Wick W, Platten M, Unterberg A, Uhl M, Abdollahi A, Debus J, Lehner B, Thomas C, Hasselblatt M, Paulus W, Hartmann C, Staszewski O, Prinz M, Hench J, Frank S, Versleijen-Jonkers YMH, Weidema ME, Mentzel T, Griewank K, de Alava E, Martin JD, Gastearena MAI, Chang KT, Low SYY, Cuevas-Bourdier A, Mittelbronn M, Mynarek M, Rutkowski S, Schuller U, Mautner VF, Schittenhelm J, Serrano J, Snuderl M, Buttner R, Klingebiel T, Buslei R, Gessler M, Wesseling P, Dinjens WNM, Brandner S, Jaunmuktane Z, Lyskjaer I, Schirmacher P, Stenzinger A, Brors B, Glimm H, Heining C, Tirado OM, Sainz-Jaspeado M, Mora J, Alonso J, Del Muro XG, Moran S, Esteller M, Benhamida JK, Ladanyi M, Wardelmann E, Antonescu C, Flanagan A, Dirksen U, Hohenberger P, Baumhoer D, Hartmann W, Vokuhl C, Flucke U, Petersen I, Mechtersheimer G, Capper D, Jones DTW, Frohling S, Pfister SM, von Deimling A. Sarcoma classification by DNA methylation profiling. Nat Commun. 2021 Jan 21;12(1):498. doi: 10.1038/s41467-020-20603-4.

    PubMed 33479225

  • Hovestadt V, Remke M, Kool M, Pietsch T, Northcott PA, Fischer R, Cavalli FM, Ramaswamy V, Zapatka M, Reifenberger G, Rutkowski S, Schick M, Bewerunge-Hudler M, Korshunov A, Lichter P, Taylor MD, Pfister SM, Jones DT. Robust molecular subgrouping and copy-number profiling of medulloblastoma from small amounts of archival tumour material using high-density DNA methylation arrays. Acta Neuropathol. 2013 Jun;125(6):913-6. doi: 10.1007/s00401-013-1126-5. Epub 2013 May 14. No abstract available.

    PubMed 23670100

  • Pajtler KW, Witt H, Sill M, Jones DT, Hovestadt V, Kratochwil F, Wani K, Tatevossian R, Punchihewa C, Johann P, Reimand J, Warnatz HJ, Ryzhova M, Mack S, Ramaswamy V, Capper D, Schweizer L, Sieber L, Wittmann A, Huang Z, van Sluis P, Volckmann R, Koster J, Versteeg R, Fults D, Toledano H, Avigad S, Hoffman LM, Donson AM, Foreman N, Hewer E, Zitterbart K, Gilbert M, Armstrong TS, Gupta N, Allen JC, Karajannis MA, Zagzag D, Hasselblatt M, Kulozik AE, Witt O, Collins VP, von Hoff K, Rutkowski S, Pietsch T, Bader G, Yaspo ML, von Deimling A, Lichter P, Taylor MD, Gilbertson R, Ellison DW, Aldape K, Korshunov A, Kool M, Pfister SM. Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups. Cancer Cell. 2015 May 11;27(5):728-43. doi: 10.1016/j.ccell.2015.04.002.

    PubMed 25965575

  • Sturm D, Orr BA, Toprak UH, Hovestadt V, Jones DTW, Capper D, Sill M, Buchhalter I, Northcott PA, Leis I, Ryzhova M, Koelsche C, Pfaff E, Allen SJ, Balasubramanian G, Worst BC, Pajtler KW, Brabetz S, Johann PD, Sahm F, Reimand J, Mackay A, Carvalho DM, Remke M, Phillips JJ, Perry A, Cowdrey C, Drissi R, Fouladi M, Giangaspero F, Lastowska M, Grajkowska W, Scheurlen W, Pietsch T, Hagel C, Gojo J, Lotsch D, Berger W, Slavc I, Haberler C, Jouvet A, Holm S, Hofer S, Prinz M, Keohane C, Fried I, Mawrin C, Scheie D, Mobley BC, Schniederjan MJ, Santi M, Buccoliero AM, Dahiya S, Kramm CM, von Bueren AO, von Hoff K, Rutkowski S, Herold-Mende C, Fruhwald MC, Milde T, Hasselblatt M, Wesseling P, Rossler J, Schuller U, Ebinger M, Schittenhelm J, Frank S, Grobholz R, Vajtai I, Hans V, Schneppenheim R, Zitterbart K, Collins VP, Aronica E, Varlet P, Puget S, Dufour C, Grill J, Figarella-Branger D, Wolter M, Schuhmann MU, Shalaby T, Grotzer M, van Meter T, Monoranu CM, Felsberg J, Reifenberger G, Snuderl M, Forrester LA, Koster J, Versteeg R, Volckmann R, van Sluis P, Wolf S, Mikkelsen T, Gajjar A, Aldape K, Moore AS, Taylor MD, Jones C, Jabado N, Karajannis MA, Eils R, Schlesner M, Lichter P, von Deimling A, Pfister SM, Ellison DW, Korshunov A, Kool M. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. Cell. 2016 Feb 25;164(5):1060-1072. doi: 10.1016/j.cell.2016.01.015.

    PubMed 26919435

  • Pisanic TR 2nd, Wang Y, Sun H, Considine M, Li L, Wang TH, Wang TL, Shih IM. Methylomic Landscapes of Ovarian Cancer Precursor Lesions. Clin Cancer Res. 2020 Dec 1;26(23):6310-6320. doi: 10.1158/1078-0432.CCR-20-0270. Epub 2020 Aug 17.

    PubMed 32817081

  • Muller D, Gyorffy B. DNA methylation-based diagnostic, prognostic, and predictive biomarkers in colorectal cancer. Biochim Biophys Acta Rev Cancer. 2022 May;1877(3):188722. doi: 10.1016/j.bbcan.2022.188722. Epub 2022 Mar 17.

    PubMed 35307512

  • Liu MC, Oxnard GR, Klein EA, Swanton C, Seiden MV; CCGA Consortium. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA. Ann Oncol. 2020 Jun;31(6):745-759. doi: 10.1016/j.annonc.2020.02.011. Epub 2020 Mar 30.

    PubMed 33506766

  • Nunes SP, Moreira-Barbosa C, Salta S, Palma de Sousa S, Pousa I, Oliveira J, Soares M, Rego L, Dias T, Rodrigues J, Antunes L, Henrique R, Jeronimo C. Cell-Free DNA Methylation of Selected Genes Allows for Early Detection of the Major Cancers in Women. Cancers (Basel). 2018 Sep 26;10(10):357. doi: 10.3390/cancers10100357.

    PubMed 30261643

  • Moran S, Martinez-Cardus A, Sayols S, Musulen E, Balana C, Estival-Gonzalez A, Moutinho C, Heyn H, Diaz-Lagares A, de Moura MC, Stella GM, Comoglio PM, Ruiz-Miro M, Matias-Guiu X, Pazo-Cid R, Anton A, Lopez-Lopez R, Soler G, Longo F, Guerra I, Fernandez S, Assenov Y, Plass C, Morales R, Carles J, Bowtell D, Mileshkin L, Sia D, Tothill R, Tabernero J, Llovet JM, Esteller M. Epigenetic profiling to classify cancer of unknown primary: a multicentre, retrospective analysis. Lancet Oncol. 2016 Oct;17(10):1386-1395. doi: 10.1016/S1470-2045(16)30297-2. Epub 2016 Aug 27.

    PubMed 27575023

  • Zhang Z, Lu Y, Vosoughi S, Levy JJ, Christensen BC, Salas LA. HiTAIC: hierarchical tumor artificial intelligence classifier traces tissue of origin and tumor type in primary and metastasized tumors using DNA methylation. NAR Cancer. 2023 Apr 19;5(2):zcad017. doi: 10.1093/narcan/zcad017. eCollection 2023 Jun.

    PubMed 37089814

  • Greco FA, Lennington WJ, Spigel DR, Hainsworth JD. Molecular profiling diagnosis in unknown primary cancer: accuracy and ability to complement standard pathology. J Natl Cancer Inst. 2013 Jun 5;105(11):782-90. doi: 10.1093/jnci/djt099. Epub 2013 May 2.

    PubMed 23641043

Questions about this trial

What is this clinical trial studying?

An observational study of Unknown Primary Tumors and DNA Methylation, run by Sun Yat-sen University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 23 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Yiyang Zhang (+8615652797092, zhangyy@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: From date of diagnosis until the date of death from any cause, assessed up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06140992, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in