Drug Sensitivity Detection of Micro Tumor (PTC) to Guide Postoperative Adjuvant Treatment Strategy of Colorectal Cancer

Official title

Vitro 3D Drug Sensitivity Detection of Micro Tumor (PTC) Combined with Tumor Whole Exon (WES) Sequencing Technology to Guide Postoperative Adjuvant Treatment Strategy and Prognosis of Colorectal Cancer

Overview

The research objectives is to compare vitro 3D drug sensitivity test results of micro tumor (PTC) with the clinical outcomes of patients, evaluate the consistency between the test results of the technology platform and the clinical prognosis, and explore the decision-making value and guiding significance of this technology in assisting the precise treatment of colorectal cancer. The completion of this study will provide real-world data support for the clinical application of micro tumor (PTC) in vitro 3D drug sensitivity detection technology, and provide more valuable reference basis for realizing the individualization and accuracy of colorectal cancer treatment and improving the clinical benefit rate.

Detailed description

The study is a multi agency prospective cohort study in China. The subjects were patients aged 18 \~ 75 years with colorectal cancer diagnosed by histopathology or cytology. They must be colorectal cancer patients who have at least one assessable tumor focus, need adjuvant therapy after radical surgery, and have not received neoadjuvant therapy， ECoG physical condition score ≤ 2 points. And they must be voluntarily participate in and sign informed consent.

The patients were randomly divided into PTC drug sensitivity test group and control group. The PTC drug sensitivity test group selected the adjuvant chemotherapy scheme according to the 3D drug sensitivity test results of micro tumor (PTC) in vitro. The control group made adjuvant chemotherapy strategy according to clinical experience. All exon (WES) data collection was used to predict postoperative survival in both groups.

The primary endpoint was the non inferiority test, and the 3-year disease-free survival rate was T-C \>- Δ

Interventions

• Drug 5-fluorouracil + formyltetrahydrofolate/Oxaliplatin + 5-fluorouracil + formyltetrahydrofolate/Irinotecan + 5-fluorouracil + formyltetrahydrofolate/Cetuximab + 5-fluorouracil + formyltetrahydrofolate
  Choose chemotherapeutic drugs（5-fluorouracil + formyltetrahydrofolate/Oxaliplatin + 5-fluorouracil + formyltetrahydrofolate/Irinotecan + 5-fluorouracil + formyltetrahydrofolate/Cetuximab + 5-fluorouracil + formyltetrahydrofolate） based on PTC drug sensitivity results.

Primary outcome measures

• The difference of 3-year disease-free survival rate of patients in both group [Time frame: 3 years]

Secondary outcome measures (9)

• The relation between TMB and clinical outcomes [Time frame: 3 years]
• The relation between MSI and clinical outcomes [Time frame: 3 years]
• The relation between dMMR and clinical outcomes [Time frame: 3 years]
• The difference of clinical outcomes of patients in both group [Time frame: 3 years]
• The difference of TTP of patients in both group [Time frame: 3 years]
• The difference of ORR of patients in both group [Time frame: three years]
• The difference of DFS of patients in both group [Time frame: 3 years]
• The difference of PFS of patients in both group [Time frame: 3 years]
• The difference of OS of patients in both group [Time frame: 3 years]

Eligibility criteria

Inclusion criteria

• Age 18 \~ 75 years old, regardless of gender
• Patients with colorectal cancer diagnosed by histopathology or cytology
• Colorectal cancer patients who need adjuvant therapy after radical surgery and have not received neoadjuvant therapy
• Having at least one assessable tumor focus
• ECoG physical condition score ≤ 2 points
• Voluntarily participate and sign informed consent

Exclusion criteria

• Patients diagnosed with metastasis
• Patients who cannot obtain tumor samples
• Pregnant and lactating women
• Patients with poor compliance
• Patients with severe cardiovascular and cerebrovascular complications who cannot receive adjuvant treatment
• Patients with other malignant tumors
• Suffering from serious mental and nervous system diseases
• The researchers believe that patients should not be selected for this study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Peking Union Medical College Hospital — Beijing

Publications

• de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000 Aug;18(16):2938-47. doi: 10.1200/JCO.2000.18.16.2938. PMID 10944126
• Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, Lin C, Leach C, Cannady RS, Cho H, Scoppa S, Hachey M, Kirch R, Jemal A, Ward E. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012 Jul-Aug;62(4):220-41. doi: 10.3322/caac.21149. Epub 2012 Jun 14. PMID 22700443
• Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Pitot HC, Alberts SR. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2004 Jan 1;22(1):23-30. doi: 10.1200/JCO.2004.09.046. Epub 2003 Dec 9. PMID 14665611
• Yin S, Xi R, Wu A, Wang S, Li Y, Wang C, Tang L, Xia Y, Yang D, Li J, Ye B, Yu Y, Wang J, Zhang H, Ren F, Zhang Y, Shen D, Wang L, Ying X, Li Z, Bu Z, Ji X, Gao X, Jia Y, Jia Z, Li N, Li Z, Ji JF, Xi JJ. Patient-derived tumor-like cell clusters for drug testing in cancer therapy. Sci Transl Med. 2020 Jun 24;12(549):eaaz1723. doi: 10.1126/scitranslmed.aaz1723. PMID 32581131
• Cassidy J, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzen F, Saltz L. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008 Apr 20;26(12):2006-12. doi: 10.1200/JCO.2007.14.9898. PMID 18421053
• Gao H, Korn JM, Ferretti S, Monahan JE, Wang Y, Singh M, Zhang C, Schnell C, Yang G, Zhang Y, Balbin OA, Barbe S, Cai H, Casey F, Chatterjee S, Chiang DY, Chuai S, Cogan SM, Collins SD, Dammassa E, Ebel N, Embry M, Green J, Kauffmann A, Kowal C, Leary RJ, Lehar J, Liang Y, Loo A, Lorenzana E, Robert McDonald E 3rd, McLaughlin ME, Merkin J, Meyer R, Naylor TL, Patawaran M, Reddy A, Roelli C, Ruddy PMID 26479923
• Qiu X, Li R, Xie G, Ning N, Wang Z, Zhou J, Liu G, Tang Q, He Z, Yang L, Lu J, Li P, Lin G. In vitro 3D drug sensitivity testing for patient-derived tumor-like cell clusters and whole-exome sequencing to personalize postoperative treatment: A study protocol for a multicenter randomized controlled trial. PLoS One. 2025 Jul 14;20(7):e0326760. doi: 10.1371/journal.pone.0326760. eCollection 2025. PMID 40658653

Identifiers

NCT: NCT05424692 · PekingUMCHPTC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗