The Culture of Advanced or Recurrent Ovarian Cancer Organoids and Drug Screening

Ovarian Neoplasms Clinical Trial

Official title:

Drug Response in Patient-derived Organoids Models of Advanced or Recurrent Ovarian Cancer, an Exploratory Research

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05290961
• Other study ID #: CQGOG0202
• Status: Recruiting
• Start date: March 9, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: August 2023
• Source: Chongqing University Cancer Hospital
• Contact: Dongling Zou, M.D.
• Phone: 13657690699
• Email: cqzl_zdl[@]163.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Most ovarian cancer will relapse after standard therapy. Patients with recurrent ovarian cancer are resistant to platinum. Due to the high heterogeneity between ovarian cancer, individual precise therapy is of great importance. The study will establish ovarian cancer organoids, whose original tissues from the patients with advanced or recurrent ovarian cancer, their tumors cannot be excised completely. The organoids will be identified at the histopathological level and gene level for evaluating the consistency with the original tumor tissue. The drug's sensitivity and specificity are detected through the organoids model. Compared with the clinical efficiency of the actual drug regimen, the efficacy of the organoid drug screening model can be assessed. The aim is to construct a precise drug screening platform for advanced and recurrent ovarian cancer patients and innovate drug research and development.

Description:

This trial is a single-arm and prospective observational study. The subjects are the advanced or recurrent ovarian cancer patients, who are planned to undergo surgery, but the neoplastic lesions can't be excised thoroughly. They voluntarily participate in the study and sign an informed consent form. General information will be collected, including name, age, address and contact information. Comprehensive physical examination will be performed. Ovarian cancer tumor markers and imaging examinations (gastroenterostomy, ultrasound / CT / MRI or PET / CT) should be taken within 4 weeks before treatment. Histopathological and genetic characteristics were analyzed in organoids and paired primary tumors to confirm whether organoids faithfully recapitulated the original tumor tissues. The sensitivity and specificity of first-line and second-line drugs from NCCN guidelines will be detected on the organoids. Ovarian cancer (CA125、HE4、CEA、CA-199) markers will be tested within one week. After the treatment period of 3 and 6 months, the short-term efficacy will be evaluated according to the efficacy evaluation standard of solid tumor (Recist1.1) (the window period is 4 weeks). Biochemical indexes, adverse reactions, and prognosis (PFS, OS) will be followed. Compared with the efficacy of the actual clinical regimen, the potency of organoid as a drug screening model will be assessed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients voluntarily participated in the study and signed informed consent;

2. The tumour cannot be excised thoroughly by surgery;

3. ECOG score = 2;

4. Expected survival >6 months;

5. Blood routine test: Hb=70g/L?WBC=3.5×109/ L ?ANC=1.5×109/L?PLT=80×109/L;

6. Both serum ALT and serum AST = 2 × ULN; blood creatinine = 1.5 × ULN;

7. Unpregnant women (negative HCG) received contraception in the study;

8. Good compliance is judged by researchers.

Exclusion Criteria:

1. Active or the uncontrol serious infections;

2. Patients with liver cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis need antiviral treatment;

3. A history of immune deficiency, including HIV positive or other acquired congenital immune deficiency diseases;

4. Chronic renal insufficiency and renal failure;

5. Myocardial infarction, severe arrhythmia and congestive heart failure (= grade 2 according to NYHA classification);

6. Autoimmune diseases, including systemic lupus erythematosus;

7. Patients take drugs that damage liver and kidney function for other complications, such as tuberculosis;

8. Patients cannot understand the experimental contents and refuse to sign the informed consent form;

9. Other concomitant serious diseases harm the health of patients or interfere with the study.

Related Conditions & MeSH terms

• Ovarian Neoplasms

Locations

Country	Name	City	State
China	Chongqing University Cancer Hospital	Chongqing	Chongqing

Sponsors (1)

Lead Sponsor	Collaborator
Chongqing University Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (14)

Bergamaschi A, Hjortland GO, Triulzi T, Sorlie T, Johnsen H, Ree AH, Russnes HG, Tronnes S, Maelandsmo GM, Fodstad O, Borresen-Dale AL, Engebraaten O. Molecular profiling and characterization of luminal-like and basal-like in vivo breast cancer xenograft models. Mol Oncol. 2009 Dec;3(5-6):469-82. doi: 10.1016/j.molonc.2009.07.003. Epub 2009 Aug 4. — View Citation

Bertotti A, Migliardi G, Galimi F, Sassi F, Torti D, Isella C, Cora D, Di Nicolantonio F, Buscarino M, Petti C, Ribero D, Russolillo N, Muratore A, Massucco P, Pisacane A, Molinaro L, Valtorta E, Sartore-Bianchi A, Risio M, Capussotti L, Gambacorta M, Siena S, Medico E, Sapino A, Marsoni S, Comoglio PM, Bardelli A, Trusolino L. A molecularly annotated platform of patient-derived xenografts ("xenopatients") identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov. 2011 Nov;1(6):508-23. doi: 10.1158/2159-8290.CD-11-0109. Epub 2011 Sep 2. — View Citation

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. — View Citation

Brancati G, Treutlein B, Camp JG. Resolving Neurodevelopmental and Vision Disorders Using Organoid Single-Cell Multi-omics. Neuron. 2020 Sep 23;107(6):1000-1013. doi: 10.1016/j.neuron.2020.09.001. — View Citation

Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong KK. Non-small-cell lung cancers: a heterogeneous set of diseases. Nat Rev Cancer. 2014 Aug;14(8):535-46. doi: 10.1038/nrc3775. Erratum In: Nat Rev Cancer. 2015 Apr;15(4):247. — View Citation

Ganesh K, Wu C, O'Rourke KP, Szeglin BC, Zheng Y, Sauve CG, Adileh M, Wasserman I, Marco MR, Kim AS, Shady M, Sanchez-Vega F, Karthaus WR, Won HH, Choi SH, Pelossof R, Barlas A, Ntiamoah P, Pappou E, Elghouayel A, Strong JS, Chen CT, Harris JW, Weiser MR, Nash GM, Guillem JG, Wei IH, Kolesnick RN, Veeraraghavan H, Ortiz EJ, Petkovska I, Cercek A, Manova-Todorova KO, Saltz LB, Lavery JA, DeMatteo RP, Massague J, Paty PB, Yaeger R, Chen X, Patil S, Clevers H, Berger MF, Lowe SW, Shia J, Romesser PB, Dow LE, Garcia-Aguilar J, Sawyers CL, Smith JJ. A rectal cancer organoid platform to study individual responses to chemoradiation. Nat Med. 2019 Oct;25(10):1607-1614. doi: 10.1038/s41591-019-0584-2. Epub 2019 Oct 7. — View Citation

Gao D, Vela I, Sboner A, Iaquinta PJ, Karthaus WR, Gopalan A, Dowling C, Wanjala JN, Undvall EA, Arora VK, Wongvipat J, Kossai M, Ramazanoglu S, Barboza LP, Di W, Cao Z, Zhang QF, Sirota I, Ran L, MacDonald TY, Beltran H, Mosquera JM, Touijer KA, Scardino PT, Laudone VP, Curtis KR, Rathkopf DE, Morris MJ, Danila DC, Slovin SF, Solomon SB, Eastham JA, Chi P, Carver B, Rubin MA, Scher HI, Clevers H, Sawyers CL, Chen Y. Organoid cultures derived from patients with advanced prostate cancer. Cell. 2014 Sep 25;159(1):176-187. doi: 10.1016/j.cell.2014.08.016. Epub 2014 Sep 4. — View Citation

Heo I, Dutta D, Schaefer DA, Iakobachvili N, Artegiani B, Sachs N, Boonekamp KE, Bowden G, Hendrickx APA, Willems RJL, Peters PJ, Riggs MW, O'Connor R, Clevers H. Modelling Cryptosporidium infection in human small intestinal and lung organoids. Nat Microbiol. 2018 Jul;3(7):814-823. doi: 10.1038/s41564-018-0177-8. Epub 2018 Jun 25. — View Citation

Rossi G, Manfrin A, Lutolf MP. Progress and potential in organoid research. Nat Rev Genet. 2018 Nov;19(11):671-687. doi: 10.1038/s41576-018-0051-9. — View Citation

Sachs N, Clevers H. Organoid cultures for the analysis of cancer phenotypes. Curr Opin Genet Dev. 2014 Feb;24:68-73. doi: 10.1016/j.gde.2013.11.012. Epub 2013 Dec 31. — View Citation

Sato T, Stange DE, Ferrante M, Vries RG, Van Es JH, Van den Brink S, Van Houdt WJ, Pronk A, Van Gorp J, Siersema PD, Clevers H. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. Gastroenterology. 2011 Nov;141(5):1762-72. doi: 10.1053/j.gastro.2011.07.050. Epub 2011 Sep 2. — View Citation

Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 2009 May 14;459(7244):262-5. doi: 10.1038/nature07935. Epub 2009 Mar 29. — View Citation

Tuveson D, Clevers H. Cancer modeling meets human organoid technology. Science. 2019 Jun 7;364(6444):952-955. doi: 10.1126/science.aaw6985. — View Citation

Zhao X, Liu Z, Yu L, Zhang Y, Baxter P, Voicu H, Gurusiddappa S, Luan J, Su JM, Leung HC, Li XN. Global gene expression profiling confirms the molecular fidelity of primary tumor-based orthotopic xenograft mouse models of medulloblastoma. Neuro Oncol. 2012 May;14(5):574-83. doi: 10.1093/neuonc/nos061. Epub 2012 Mar 29. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	Progression-free survival means the duration from enrollment to disease progression or death.	2 years
Secondary	Overall survival	Overall survival means the duration from enrollment to death due to any cause. The last follow-up time is calculated as the death time for subjects who lost follow-up.	2 years