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Pancreatic CancerNCT05196334

Pharmacotyping of Pancreatic Patient-derived Organoids

An observational study of Pancreatic Cancer, run by Herlev Hospital at 1 site in Denmark.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

EUS-FNB samples will be used for organoid cultures, which will be co-cultured with cancer associated fibroblasts derived from the surrounding stroma of the lesion. The organoid cultures will be used for pharmacotyping using relevant chemotherapeutic agents used in the clinic, and the organoid's response compared with… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pancreatic Cancer
How many people
88 participants
Where
1 siteDenmark
Study dates
1 Jul 2021to 31 Aug 2025
Phase
Observational
Are there results?
None posted in the registry

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

Study population: Patients with histopathological confirmation of pancreatic ductal adenocarcimona, ineligible for surgery, planned to start standard first line treatment

Who may be able to join

  • Signed informed consent
  • Histopathological confirmation of PDAC and planned standard first-line treatment prior to entering this study OR Patients suspected of primary locally advanced, non-metastatic PDAC based on cross-sectional imaging undergoing diagnostic standard of care (SOC) EUS-FNB procedure
  • Age > 18 years and older
  • Life expectancy greater than 3 months
  • ECOG/WHO Performance Status (PS) 0-1
  • Patients must have normal organ and marrow function as defined below:
Show all 11Show fewer
  • White blood cell count (WBC) ≥ 3 x 10⁹/L
  • Platelet count ≥ 100 x 10⁹/L
  • Serum bilirubin ≤1.5 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin ≤ 50 mmol/L)
  • PP ≥ 40 or INR ≤ 1.5
  • Serum creatinine ≤ 1.5 x ULN or CrCl ≥ 40 mL/min (using the Cockcroft-Gault formula)

Who cannot join

  • Contraindications for nurse administered propofol sedation (NAPS)
  • Contraindications for EUS-FNB procedure

Trial locations and contacts

1 site in 1 country.

Pia H Klausen, PhD contact

+4535453545

pia.helene.klausen.01@regionh.dk

Simon E Grutzmeier, MD contact

+4538683868

simon.eban.grutzmeier@regionh.dk

Denmark1 site, 1 recruiting

  • Endoscopy Unit, Herlev Hospital

    Herlev, Copenhagen, 2730

    Simon E Grutzmeier, MD, +4538683868, simon.eban.grutzmeier@regionh.dk

    Recruiting

Other trials in Denmark

About this study

Official title: Pharmacotyping of Patient-derived Pancreatic Cancer Organoids From Endoscopic Ultrasound-guided Biopsy as a Tool for Predicting Oncological Response

EUS-FNB samples will be used for organoid cultures, which will be co-cultured with cancer associated fibroblasts derived from the surrounding stroma of the lesion. The organoid cultures will be used for pharmacotyping using relevant chemotherapeutic agents used in the clinic, and the organoid's response compared with the patient's response.

Read the detailed description

Aim: To use organoids cultured from diagnostic endoscopic ultrasound (EUS)-guided fine needle biopsy (FNB) samples from patients with pancreatic ductal adenocarcinoma (PDAC) for pharmacotyping.

Patients will be included at Herlev Hospital. EUS-FNB will be performed using a standard 19 or 22-gauge FNB needle. Oncological treatment administration and evaluation of treatment response will be performed by physicians at the Department of Oncology, Herlev Hospital as per current standard of care. Following EUS-FNB procedure, the tissue is immediately transferred to basal medium and epithelial cells as well as CAFs released by digestion and epithelial cells cultured in Matrigel. Following expansion of the organoids and prior to pharmacotyping, next generation sequencing (NGS) analysis will be performed on both the baseline and the organoid sections to validate if the outgrown organoids correspond to the cancer cells from the baseline sample.

Organoid co-cultures are exposed to six to ten different drug concentrations ranging from 10-12-10-4 M (depending on the individual drug properties). Systemic agents and combinations used in the standard clinical practise will be used. Computed tomography (CT) scan of the thorax and abdomen are performed at baseline (within 28 days prior to first study drug administration) to assess efficacy of the drugs in patients.

Being tested
No intervention
Keywords
organoid, personalized medicine
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • No interventionOther

    No intervention

What is being measured

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

  1. Measurement of organoid's response to therapy

    Response of patient derived organoids to standard chemotherapeutic agents used for treatment of patients with pancreatic cancer

    Measured: Organoid co-cultures will be established and pharmacotyped in a timeframe of 2-4 weeks.

  2. Validation of patient's response to therapy

    Computed tomography (CT) scan of the thorax and abdomen are performed at baseline (within 28 days prior to first study drug administration) to assess efficacy of the drugs in patients.

    Measured: 3 months follow up

  3. Comparison between organoid's and patient's response

    The response measured in the pharmacoscreen of organoids will be compared with the patient's response

    Measured: 4 months

Timeline

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

  1. First posted19 Jan 2022
  2. Study start1 Jul 2021
  3. Primary completion30 Aug 2025 (estimated)
  4. Study completion31 Aug 2025 (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
88 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05196334
Sponsor's protocol ID
Pancreatic organoid protocol
Status last verified
Oct 2024
First submitted
14 Oct 2021
Last updated
3 Oct 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13. doi: 10.1200/JCO.1997.15.6.2403.

    PubMed 9196156

  • Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25. doi: 10.1056/NEJMoa1011923.

    PubMed 21561347

  • Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16.

    PubMed 24131140

  • Boj SF, Hwang CI, Baker LA, Chio II, Engle DD, Corbo V, Jager M, Ponz-Sarvise M, Tiriac H, Spector MS, Gracanin A, Oni T, Yu KH, van Boxtel R, Huch M, Rivera KD, Wilson JP, Feigin ME, Ohlund D, Handly-Santana A, Ardito-Abraham CM, Ludwig M, Elyada E, Alagesan B, Biffi G, Yordanov GN, Delcuze B, Creighton B, Wright K, Park Y, Morsink FH, Molenaar IQ, Borel Rinkes IH, Cuppen E, Hao Y, Jin Y, Nijman IJ, Iacobuzio-Donahue C, Leach SD, Pappin DJ, Hammell M, Klimstra DS, Basturk O, Hruban RH, Offerhaus GJ, Vries RG, Clevers H, Tuveson DA. Organoid models of human and mouse ductal pancreatic cancer. Cell. 2015 Jan 15;160(1-2):324-38. doi: 10.1016/j.cell.2014.12.021. Epub 2014 Dec 31.

    PubMed 25557080

  • Tiriac H, Bucobo JC, Tzimas D, Grewel S, Lacomb JF, Rowehl LM, Nagula S, Wu M, Kim J, Sasson A, Vignesh S, Martello L, Munoz-Sagastibelza M, Somma J, Tuveson DA, Li E, Buscaglia JM. Successful creation of pancreatic cancer organoids by means of EUS-guided fine-needle biopsy sampling for personalized cancer treatment. Gastrointest Endosc. 2018 Jun;87(6):1474-1480. doi: 10.1016/j.gie.2017.12.032. Epub 2018 Jan 9.

    PubMed 29325707

  • Seppala TT, Zimmerman JW, Sereni E, Plenker D, Suri R, Rozich N, Blair A, Thomas DL 2nd, Teinor J, Javed A, Patel H, Cameron JL, Burns WR, He J, Tuveson DA, Jaffee EM, Eshleman J, Szabolcs A, Ryan DP, Ting DT, Wolfgang CL, Burkhart RA. Patient-derived Organoid Pharmacotyping is a Clinically Tractable Strategy for Precision Medicine in Pancreatic Cancer. Ann Surg. 2020 Sep 1;272(3):427-435. doi: 10.1097/SLA.0000000000004200.

    PubMed 32657929

  • Tiriac H, Belleau P, Engle DD, Plenker D, Deschenes A, Somerville TDD, Froeling FEM, Burkhart RA, Denroche RE, Jang GH, Miyabayashi K, Young CM, Patel H, Ma M, LaComb JF, Palmaira RLD, Javed AA, Huynh JC, Johnson M, Arora K, Robine N, Shah M, Sanghvi R, Goetz AB, Lowder CY, Martello L, Driehuis E, LeComte N, Askan G, Iacobuzio-Donahue CA, Clevers H, Wood LD, Hruban RH, Thompson E, Aguirre AJ, Wolpin BM, Sasson A, Kim J, Wu M, Bucobo JC, Allen P, Sejpal DV, Nealon W, Sullivan JD, Winter JM, Gimotty PA, Grem JL, DiMaio DJ, Buscaglia JM, Grandgenett PM, Brody JR, Hollingsworth MA, O'Kane GM, Notta F, Kim E, Crawford JM, Devoe C, Ocean A, Wolfgang CL, Yu KH, Li E, Vakoc CR, Hubert B, Fischer SE, Wilson JM, Moffitt R, Knox J, Krasnitz A, Gallinger S, Tuveson DA. Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer. Cancer Discov. 2018 Sep;8(9):1112-1129. doi: 10.1158/2159-8290.CD-18-0349. Epub 2018 May 31.

    PubMed 29853643

  • Vlachogiannis G, Hedayat S, Vatsiou A, Jamin Y, Fernandez-Mateos J, Khan K, Lampis A, Eason K, Huntingford I, Burke R, Rata M, Koh DM, Tunariu N, Collins D, Hulkki-Wilson S, Ragulan C, Spiteri I, Moorcraft SY, Chau I, Rao S, Watkins D, Fotiadis N, Bali M, Darvish-Damavandi M, Lote H, Eltahir Z, Smyth EC, Begum R, Clarke PA, Hahne JC, Dowsett M, de Bono J, Workman P, Sadanandam A, Fassan M, Sansom OJ, Eccles S, Starling N, Braconi C, Sottoriva A, Robinson SP, Cunningham D, Valeri N. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science. 2018 Feb 23;359(6378):920-926. doi: 10.1126/science.aao2774.

    PubMed 29472484

  • Broutier L, Mastrogiovanni G, Verstegen MM, Francies HE, Gavarro LM, Bradshaw CR, Allen GE, Arnes-Benito R, Sidorova O, Gaspersz MP, Georgakopoulos N, Koo BK, Dietmann S, Davies SE, Praseedom RK, Lieshout R, IJzermans JNM, Wigmore SJ, Saeb-Parsy K, Garnett MJ, van der Laan LJ, Huch M. Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat Med. 2017 Dec;23(12):1424-1435. doi: 10.1038/nm.4438. Epub 2017 Nov 13.

    PubMed 29131160

  • Votanopoulos KI, Mazzocchi A, Sivakumar H, Forsythe S, Aleman J, Levine EA, Skardal A. Appendiceal Cancer Patient-Specific Tumor Organoid Model for Predicting Chemotherapy Efficacy Prior to Initiation of Treatment: A Feasibility Study. Ann Surg Oncol. 2019 Jan;26(1):139-147. doi: 10.1245/s10434-018-7008-2. Epub 2018 Nov 9.

    PubMed 30414038

  • Ohlund D, Handly-Santana A, Biffi G, Elyada E, Almeida AS, Ponz-Sarvise M, Corbo V, Oni TE, Hearn SA, Lee EJ, Chio II, Hwang CI, Tiriac H, Baker LA, Engle DD, Feig C, Kultti A, Egeblad M, Fearon DT, Crawford JM, Clevers H, Park Y, Tuveson DA. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J Exp Med. 2017 Mar 6;214(3):579-596. doi: 10.1084/jem.20162024. Epub 2017 Feb 23.

    PubMed 28232471

  • Seino T, Kawasaki S, Shimokawa M, Tamagawa H, Toshimitsu K, Fujii M, Ohta Y, Matano M, Nanki K, Kawasaki K, Takahashi S, Sugimoto S, Iwasaki E, Takagi J, Itoi T, Kitago M, Kitagawa Y, Kanai T, Sato T. Human Pancreatic Tumor Organoids Reveal Loss of Stem Cell Niche Factor Dependence during Disease Progression. Cell Stem Cell. 2018 Mar 1;22(3):454-467.e6. doi: 10.1016/j.stem.2017.12.009. Epub 2018 Jan 11.

    PubMed 29337182

  • Engholm G, Ferlay J, Christensen N, Bray F, Gjerstorff ML, Klint A, Kotlum JE, Olafsdottir E, Pukkala E, Storm HH. NORDCAN--a Nordic tool for cancer information, planning, quality control and research. Acta Oncol. 2010 Jun;49(5):725-36. doi: 10.3109/02841861003782017.

    PubMed 20491528

Questions about this trial

What is this clinical trial studying?

An observational study of Pancreatic Cancer, run by Herlev Hospital at 1 site in Denmark.

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 11 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 3 Oct 2024. 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 Denmark. 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?

Results are not available in the source record.

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

Contact Pia H Klausen, PhD (+4535453545, pia.helene.klausen.01@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Measurement of organoid's response to therapy (time frame: Organoid co-cultures will be established and pharmacotyped in a timeframe of 2-4 weeks.). The study lists 3 primary outcomes in all. 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 NCT05196334, which also lists 13 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 3 Oct 2024.

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