The Clinical Efficacy of Drug Sensitive Neoadjuvant Chemotherapy Based on Organoid Versus Traditional Neoadjuvant Chemotherapy in Advanced Rectal Cancer

NCT05352165 | Unknown DMC

• 1 other identifier: MISC-WXXR-001
• Study Type: interventional
• Target: 192
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective multicenter randomized controlled trial study. According to the enrollment criteria, patients with locally advanced rectal cancer who need neoadjuvant therapy before radical surgery were randomly divided into the organoids drug sensitivity group and the standard whole-course neoadjuvant therapy group. The Organoids drug sensitivity group was treated with personalized neoadjuvant therapy under the guidance of tumor organoids drug sensitivity technology combined with standard long-term radiotherapy. The standard whole-course neoadjuvant therapy group was treated with neoadjuvant simultaneous radiotherapy and chemotherapy (Total Neoadjuvant Therapy, TNT) based on guidelines and clinical experience. The tumor pathological complete remission rate (pCR), postoperative complication rate, postoperative tumor withdrawal grade, postoperative recurrence rate, treatment tolerance rate, R0 resection rate, and sphincter preservation rate were observed and compared.

Conditions

Neoadjuvant Therapy

Keywords

neoadjuvant therapy; organoid drug sensitivity; advanced rectal cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response

  Neoadjuvant therapy and postoperative pathology confirmed that the primary tumor was in complete remission (stage ypT0) and had no residual tumor cells, regardless of whether the regional lymph nodes were involved or not.

  3 years

Secondary Outcomes (7)

• Postoperative complication

  3 years

• Tumor Regression Grading

  3 years

• Local recurrence

  3 years

• Distant metastasis

  3 years

• Treatment tolerance rate

  3 years

Study Arms (6)

standard long-term therapy

EXPERIMENTAL

The standard whole-course neoadjuvant therapy group was treated with neoadjuvant simultaneous radiotherapy and chemotherapy (Total Neoadjuvant Therapy, TNT) based on guidelines and clinical experience.

Drug: standard long-term therapy; Drug: FOLFOX and standard long-term radiotherapy; Drug: FOLFIRI and standard long-term radiotherapy; Drug: 5-FU and standard long-term radiotherapy; Drug: 5-FU and pembrolizumab and standard long-term radiotherapy; Drug: Other individualized treatments

FOLFOX and standard long-term radiotherapy

ACTIVE COMPARATOR

FOLFOX and standard long-term radiotherapy based on organoids drug sensitivity

Drug: standard long-term therapy; Drug: FOLFOX and standard long-term radiotherapy; Drug: FOLFIRI and standard long-term radiotherapy; Drug: 5-FU and standard long-term radiotherapy; Drug: 5-FU and pembrolizumab and standard long-term radiotherapy; Drug: Other individualized treatments

FOLFIRI and standard long-term radiotherapy

ACTIVE COMPARATOR

FOLFIRI and standard long-term radiotherapy based on organoids drug sensitivity

Drug: standard long-term therapy; Drug: FOLFOX and standard long-term radiotherapy; Drug: FOLFIRI and standard long-term radiotherapy; Drug: 5-FU and standard long-term radiotherapy; Drug: 5-FU and pembrolizumab and standard long-term radiotherapy; Drug: Other individualized treatments

5-FU and standard long-term radiotherapy

ACTIVE COMPARATOR

5-FU and standard long-term radiotherapy based on organoids drug sensitivity

Drug: standard long-term therapy; Drug: FOLFOX and standard long-term radiotherapy; Drug: FOLFIRI and standard long-term radiotherapy; Drug: 5-FU and standard long-term radiotherapy; Drug: 5-FU and pembrolizumab and standard long-term radiotherapy; Drug: Other individualized treatments

5-FU and pembrolizumab and standard long-term radiotherapy

ACTIVE COMPARATOR

5-FU and pembrolizumab and standard long-term radiotherapy based on organoids drug sensitivity

Drug: standard long-term therapy; Drug: FOLFOX and standard long-term radiotherapy; Drug: FOLFIRI and standard long-term radiotherapy; Drug: 5-FU and standard long-term radiotherapy; Drug: 5-FU and pembrolizumab and standard long-term radiotherapy; Drug: Other individualized treatments

Other individualized treatments

ACTIVE COMPARATOR

Other individualized treatments based on organoids drug sensitivity

Drug: standard long-term therapy; Drug: FOLFOX and standard long-term radiotherapy; Drug: FOLFIRI and standard long-term radiotherapy; Drug: 5-FU and standard long-term radiotherapy; Drug: 5-FU and pembrolizumab and standard long-term radiotherapy; Drug: Other individualized treatments

Interventions

standard long-term therapy DRUG

The standard whole-course neoadjuvant therapy group was treated with neoadjuvant simultaneous radiotherapy and chemotherapy (Total Neoadjuvant Therapy, TNT) based on guidelines and clinical experience.

5-FU and pembrolizumab and standard long-term radiotherapy; 5-FU and standard long-term radiotherapy; FOLFIRI and standard long-term radiotherapy; FOLFOX and standard long-term radiotherapy; Other individualized treatments; standard long-term therapy

FOLFOX and standard long-term radiotherapy DRUG

FOLFOX and standard long-term radiotherapy based on organoids drug sensitivity

5-FU and pembrolizumab and standard long-term radiotherapy; 5-FU and standard long-term radiotherapy; FOLFIRI and standard long-term radiotherapy; FOLFOX and standard long-term radiotherapy; Other individualized treatments; standard long-term therapy

FOLFIRI and standard long-term radiotherapy DRUG

FOLFIRI and standard long-term radiotherapy based on organoids drug sensitivity

5-FU and pembrolizumab and standard long-term radiotherapy; 5-FU and standard long-term radiotherapy; FOLFIRI and standard long-term radiotherapy; FOLFOX and standard long-term radiotherapy; Other individualized treatments; standard long-term therapy

5-FU and standard long-term radiotherapy DRUG

5-FU and standard long-term radiotherapy based on organoids drug sensitivity

5-FU and pembrolizumab and standard long-term radiotherapy; 5-FU and standard long-term radiotherapy; FOLFIRI and standard long-term radiotherapy; FOLFOX and standard long-term radiotherapy; Other individualized treatments; standard long-term therapy

5-FU and pembrolizumab and standard long-term radiotherapy DRUG

5-FU and pembrolizumab and standard long-term radiotherapy based on organoids drug sensitivity

5-FU and pembrolizumab and standard long-term radiotherapy; 5-FU and standard long-term radiotherapy; FOLFIRI and standard long-term radiotherapy; FOLFOX and standard long-term radiotherapy; Other individualized treatments; standard long-term therapy

Other individualized treatments DRUG

Other individualized treatments based on organoids drug sensitivity

5-FU and pembrolizumab and standard long-term radiotherapy; 5-FU and standard long-term radiotherapy; FOLFIRI and standard long-term radiotherapy; FOLFOX and standard long-term radiotherapy; Other individualized treatments; standard long-term therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) Age: 18-75. 2) qualitative diagnosis: adenocarcinoma was confirmed by enteroscopic biopsy. 3) Localization diagnosis: the tumor is located in the rectum (the distance between the tumor and the anal margin ≤ 12cm).
• \) plain scan of thoracoabdominal pelvis and enhanced CT or MRI evaluation of rectal cancer staging:
• The primary tumor invades the muscular layer of the intestinal wall into the surrounding well-known structure, with or without lymph node metastasis in the proper rectal fascia.
• b. TNM clinical or pathological stage of tumor: T3-T4N0-2M0. 5) physical condition (ECOG) score ≤ 1. 6) all patients agreed to receive adjuvant chemotherapy for 3 to 6 months after operation.
• \) sign informed consent and participate in the project voluntarily.

You may not qualify if:

• \) simultaneous or metachronous multiple primary malignant tumors. 2) preoperative imaging examination or pathological results showed that:
• Lateral lymph node metastasis. b. Distant organ metastasis. 3) previous history of malignant tumors. 4) abnormal function of heart, lung, liver, kidney, hematopoiesis and bone marrow reserve, which can not tolerate neoadjuvant therapy and operation.
• \) have mental illness or other serious cardiovascular disease. 6) pregnant or lactating women. 7) Emergency surgery (perforation, bleeding, intestinal obstruction, etc.). 8) BRAF mutation was found by gene detection.

Sponsors & Collaborators

• Shanghai Minimally Invasive Surgery Center: lead
• Shanghai OneTar Biomedicine Co., Ltd.: collaborator
• Ruijin Hospital: collaborator

Related Publications (7)

• Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021 Jan;71(1):7-33. doi: 10.3322/caac.21654. Epub 2021 Jan 12.

  PMID: 33433946 BACKGROUND

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 BACKGROUND

• Cao W, Chen HD, Yu YW, Li N, Chen WQ. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J (Engl). 2021 Mar 17;134(7):783-791. doi: 10.1097/CM9.0000000000001474.

  PMID: 33734139 BACKGROUND

• Ludmir EB, Palta M, Willett CG, Czito BG. Total neoadjuvant therapy for rectal cancer: An emerging option. Cancer. 2017 May 1;123(9):1497-1506. doi: 10.1002/cncr.30600. Epub 2017 Mar 10.

  PMID: 28295220 BACKGROUND

• Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, Kumar AS, Oommen S, Coutsoftides T, Hunt SR, Stamos MJ, Ternent CA, Herzig DO, Fichera A, Polite BN, Dietz DW, Patil S, Avila K; Timing of Rectal Cancer Response to Chemoradiation Consortium. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015 Aug;16(8):957-66. doi: 10.1016/S1470-2045(15)00004-2. Epub 2015 Jul 14.

  PMID: 26187751 BACKGROUND

• Shamir ER, Ewald AJ. Three-dimensional organotypic culture: experimental models of mammalian biology and disease. Nat Rev Mol Cell Biol. 2014 Oct;15(10):647-64. doi: 10.1038/nrm3873. Epub 2014 Sep 17.

  PMID: 25237826 BACKGROUND

• 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.

  PMID: 19329995 BACKGROUND

MeSH Terms

Interventions

Folfox protocol; Fluorouracil; pembrolizumab

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jing Sun, PhD

  Shanghai Minimally Invasive Surgery Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jing Sun, PhD

CONTACT

+86-21-64370045; sj11788@rjh.com.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective multicenter multi-arm umbrella clinical study.

Study Record Dates

• First Submitted: April 22, 2022
• First Posted: April 28, 2022
• Study Start: January 1, 2023
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: April 28, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share