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

NCT ID: NCT05352165

Last Updated: 2022-04-28

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 192 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2025-12-31

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.

Detailed Description

Based on the need for individualized treatment in the era of precision medicine, an in vitro model that can accurately predict the response of patients to treatment is urgently needed, so that suitable patients can receive effective treatment and patients whose treatments are ineffective can avoid adverse reactions. The emergence of tumor organoids technology makes this vision possible.

Tumor-organoid (Patient-Derived Organoids, PDOs) is a kind of micro-organ with a three-dimensional structure, which is cultivated in the environment of 3D matrix glue in vitro. Based on the individualized neoadjuvant therapy based on the drug sensitivity technology of tumor-organoid, the best neoadjuvant therapy can be selected and the clinical efficacy and drug tolerance can be quickly predicted, which is of great significance in the field of accurate tumor therapy. The preliminary study of our group also completed the organ-like library of more than 100 patients with local advanced rectal cancer. It was proved that the organoids of the organoids library had high homology with the original tumor tissue, and the detection period of drug sensitivity of organoids was less than 2 weeks, which was much less than 2 months of PDX drug sensitivity technology in mice, which did not affect the time window of clinical drug treatment, and the results of drug sensitivity were basically consistent with the clinical efficacy.

Therefore, we have reason to believe that tumor organoids chemosensitivity technology, as an economical, high-throughput, and efficient technology for tumor research, is expected to play an important role in clinical individualized treatment of tumors.

Our previous study found that tumor-based organoids drug sensitivity technology can be used as an effective and reliable clinical assistant tool to guide and assist doctors to formulate the best treatment strategy for tumor patients. Personalized neoadjuvant therapy has better clinical efficacy than standard whole-course neoadjuvant therapy.

Therefore, in this study, through a prospective, multicenter, multi-arm umbrella clinical study, patients with locally advanced rectal cancer who need neoadjuvant therapy are randomly divided into two groups: the organoids drug sensitivity group and the standard whole-course neoadjuvant therapy group. To compare the clinical efficacy of personalized neoadjuvant therapy based on tumor organoids chemosensitivity combined with standard long-term radiotherapy with the clinical efficacy of standard whole-course neoadjuvant therapy in locally advanced rectal cancer. This technology can be used in the clinical use of advanced rectal cancer new auxiliary decision-making system so that the standardization of comprehensive treatment of rectal cancer can be implemented in China, which is of great significance for the development of the national economy and the improvement of medical level in China.

Conditions

Neoadjuvant Therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

standard long-term therapy

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.

Group Type: EXPERIMENTAL

standard long-term therapy

Intervention Type: 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.

FOLFOX and standard long-term radiotherapy

Intervention Type: DRUG

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

FOLFIRI and standard long-term radiotherapy

Intervention Type: DRUG

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

5-FU and standard long-term radiotherapy

Intervention Type: DRUG

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

5-FU and pembrolizumab and standard long-term radiotherapy

Intervention Type: DRUG

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

Other individualized treatments

Intervention Type: DRUG

Other individualized treatments based on organoids drug sensitivity

FOLFOX and standard long-term radiotherapy

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

Group Type: ACTIVE_COMPARATOR

standard long-term therapy

Intervention Type: 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.

FOLFOX and standard long-term radiotherapy

Intervention Type: DRUG

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

FOLFIRI and standard long-term radiotherapy

Intervention Type: DRUG

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

5-FU and standard long-term radiotherapy

Intervention Type: DRUG

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

5-FU and pembrolizumab and standard long-term radiotherapy

Intervention Type: DRUG

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

Other individualized treatments

Intervention Type: DRUG

Other individualized treatments based on organoids drug sensitivity

FOLFIRI and standard long-term radiotherapy

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

Group Type: ACTIVE_COMPARATOR

standard long-term therapy

Intervention Type: 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.

FOLFOX and standard long-term radiotherapy

Intervention Type: DRUG

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

FOLFIRI and standard long-term radiotherapy

Intervention Type: DRUG

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

5-FU and standard long-term radiotherapy

Intervention Type: DRUG

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

5-FU and pembrolizumab and standard long-term radiotherapy

Intervention Type: DRUG

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

Other individualized treatments

Intervention Type: DRUG

Other individualized treatments based on organoids drug sensitivity

5-FU and standard long-term radiotherapy

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

Group Type: ACTIVE_COMPARATOR

standard long-term therapy

Intervention Type: 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.

FOLFOX and standard long-term radiotherapy

Intervention Type: DRUG

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

FOLFIRI and standard long-term radiotherapy

Intervention Type: DRUG

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

5-FU and standard long-term radiotherapy

Intervention Type: DRUG

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

5-FU and pembrolizumab and standard long-term radiotherapy

Intervention Type: DRUG

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

Other individualized treatments

Intervention Type: DRUG

Other individualized treatments based on organoids drug sensitivity

5-FU and pembrolizumab and standard long-term radiotherapy

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

Group Type: ACTIVE_COMPARATOR

standard long-term therapy

Intervention Type: 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.

FOLFOX and standard long-term radiotherapy

Intervention Type: DRUG

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

FOLFIRI and standard long-term radiotherapy

Intervention Type: DRUG

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

5-FU and standard long-term radiotherapy

Intervention Type: DRUG

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

5-FU and pembrolizumab and standard long-term radiotherapy

Intervention Type: DRUG

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

Other individualized treatments

Intervention Type: DRUG

Other individualized treatments based on organoids drug sensitivity

Other individualized treatments

Other individualized treatments based on organoids drug sensitivity

Group Type: ACTIVE_COMPARATOR

standard long-term therapy

Intervention Type: 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.

FOLFOX and standard long-term radiotherapy

Intervention Type: DRUG

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

FOLFIRI and standard long-term radiotherapy

Intervention Type: DRUG

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

5-FU and standard long-term radiotherapy

Intervention Type: DRUG

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

5-FU and pembrolizumab and standard long-term radiotherapy

Intervention Type: DRUG

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

Other individualized treatments

Intervention Type: DRUG

Other individualized treatments based on organoids drug sensitivity

Interventions

standard long-term therapy

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.

Intervention Type: DRUG

FOLFOX and standard long-term radiotherapy

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

Intervention Type: DRUG

FOLFIRI and standard long-term radiotherapy

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

Intervention Type: DRUG

5-FU and standard long-term radiotherapy

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

Intervention Type: DRUG

5-FU and pembrolizumab and standard long-term radiotherapy

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

Intervention Type: DRUG

Other individualized treatments

Other individualized treatments based on organoids drug sensitivity

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1) 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).

4) 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.

7) sign informed consent and participate in the project voluntarily.

Exclusion Criteria

• 1) 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.

5) 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai OneTar Biomedicine Co., Ltd.

UNKNOWN

Sponsor Role: collaborator

Ruijin Hospital

OTHER

Sponsor Role: collaborator

Shanghai Minimally Invasive Surgery Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jing Sun, PhD

Role: PRINCIPAL_INVESTIGATOR

Shanghai Minimally Invasive Surgery Center

Central Contacts

Jing Sun, PhD

Role: CONTACT

sj11788@rjh.com.cn

+86-21-64370045

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Other Identifiers

MISC-WXXR-001

Identifier Type: -

Identifier Source: org_study_id