Rectal Artery Infusion Chemotherapy Combined With Anti-PD1 Antibody for MSS LARC

NCT05307198 | Unknown Phase 2

• 1 other identifier: Jun Li
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to explore whether rectal artery infusion chemotherapy combined with anti-PD1 antibody is an effective neoadjuvant therapy for the microsatellite stable locally advanced rectal cancer.

Conditions

Rectal Neoplasms

Outcome Measures

Primary Outcomes (1)

• pCR rate

  the pathological complete remission rate of the rectal carcinoma

  1 day of postoperative pathological examination.

Secondary Outcomes (7)

• DFS

  From date of first chemotherapy until the date of first documented recurrence of tumor or date of death from any cause，whichever came first，assessed up to 36 months.

• AE

  From date of first chemotherapy until the date of patients were discharged from hospital after receiving TME operation, up to 20 weeks

• Surgical Complication

  within 30 days since operation

• low anterior resection syndrome score

  3 months after operation; 6 months after operation;12 months after operation

• Concentration of FLT3LG

  blood test of FLT3LG at baseline , pre-intervention of neoadjuvant chemotherapy, pre-intervention of artery infusion chemotherapy and pre-surgery.

Study Arms (1)

Rectal Artery Infusion Chemotherapy

EXPERIMENTAL

Patients receive 2 cycles of Capecitabine and Oxaliplatin (CapeOx) chemotherapy and evaluated with rectum Magnetic Resonance Imaging (MRI). Patients with more than 20% regression of maximum diameter of rectal tumor in MRI image will entry into next step of rectal artery infusion of Oxaliplatin and oral Capecitabine（1000mg/㎡）with anti-PD1 antibody（200mg）every 3 weeks for 2 cycles.Then those patients will receive rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with TME.

Drug: Oxaliplatin; Procedure: Rectectomy; Drug: Capecitabine; Drug: Anti-PD-1 monoclonal antibody

Interventions

Oxaliplatin DRUG

Drug: Oxaliplatin Oxaliplatin 130mg/m2 for inducing chemotherapy in Day 1 every 3 weeks and repeat for two cycles. The dose of oxaliplatin used for rectal artery infusion was uncertain because there were no previous study. We design this study with Oxaliplatin 85mg/㎡for rectal artery infusion chemotherapy in Day 1 every 3 weeks and repeat for 2 cycles, based on intravenous chemotherapy regimens recommended by NCCN（mFolfox6）.If there were severe side effects caused by oxaliplatin observed within first 5 patients, we would decreasing the dose of oxaliplatin depending on the multidisciplinary discussion of researchers. We acknowledged that our study did not determine the most appropriate dosage of oxaliplatin used for artery infusion, but rather performed a novel therapeutic method for microsatellite stable locally advanced rectal cancer.

Rectal Artery Infusion Chemotherapy

Rectectomy PROCEDURE

Include anterior resection or abdominoperineal resection by open or laparoscopy with Total Mesorectal Excision (TME).

Rectal Artery Infusion Chemotherapy

Capecitabine DRUG

Oral Capecitabine 1000 mg/m2 twice daily combined with oxaliplatin chemotherapy in Day 1 to Day 14 every 3 weeks and repeat for 4 cycles.

Rectal Artery Infusion Chemotherapy

Anti-PD-1 monoclonal antibody DRUG

Anti-PD1 antibody 200mg/m2 in Day 2 after Rectal Artery Infusion Chemotherapy. Repeat every 3 weeks for 2 cycles.

Also known as: Sintilimab

Rectal Artery Infusion Chemotherapy

Eligibility Criteria

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

You may qualify if:

• Pathologically diagnosed rectal adenocarcinoma
• Age ≥18 years old and ≤75 years old
• MRI stage T3-4aNany and TanyN1-2, but not T4b and no distant metastasis
• Life expectancy of 1 year The above
• Informed consent, no contraindications to chemotherapy exist
• The distance from the lower edge of the tumor to the anus is between 5cm to 12cm by MRI

You may not qualify if:

• Refused to participate in this study
• Multifocal colorectal cancer
• Past history of malignant tumors, except for basal cell carcinoma/papillary thyroid carcinoma/various types of carcinoma in situ
• Unable to receive chemotherapy , such as but not limited to bone marrow suppression, etc
• Major organ diseases (such as but not limited to COPD, coronary heart disease and renal insufficiency, etc.) acute attack and or severe acute infectious diseases (such as but not limited to hepatitis, pneumonia and myocarditis, etc.), ASA score\> 3
• Mental disorder or illiteracy or language and communication barriers cannot understand the research plan
• There are contraindications to arterial puncture, such as but not limited to severe arteriosclerosis or even atresia, coagulation dysfunction, long-term use of anticoagulant drugs and cannot be stopped, etc
• Rectal tumor has obstruction or high risk of obstruction and or there is bleeding and/or perforation
• Peripheral sensory nerve disorder, unable to receive oxaliplatin chemotherapy
• Lateral pelvic lymph node metastasis (mainly supplied by internal iliac artery)
• Pregnancy or breastfeeding
• Unable to accept MRI examination
• Consecutive use of glucocorticoids for more than 3 days within 1 month before signing the consent form
• Tumor directly invades or adheres to adjacent organs、structures(T4b) or tumor invaded MRF（Mesoretal Fascia）
• Other scenarios deemed inappropriate by the investigators

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Oxaliplatin; Capecitabine; spartalizumab; sintilimab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Jun Li, MD

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  STUDY DIRECTOR

Central Study Contacts

Li Jun, MD

CONTACT

+86 13777878061; 2307016@zju.edu.cn

Jiao Yurong

CONTACT

+86 13732206364; jiaoyurong@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The pCR rate of neoadjuvant chemoradiotherapy is about 20% (null hypothesis). Assuming that the pCR of the RAIC scheme in this study would be in the range of 15%-35%. Using Simon's two-stage design, a total of 37 patients would provide 80% power at a one sided 5% alpha level. Considering the drop rate of 10%, 38 patients would be included (64 cases to be screened) in this study. 10 cases (17 cases were screened) and 28 cases (47 cases were screened) would be included in the first and second stages, respectively. If the number of patients with pCR in the first stage is less than 2, the study will be terminated. If the number of patients with pCR in the first stage is more than 2, a second-stage trial will be performed. If the total number of patients with pCR is more than 9, the effective remission rate of the RAIC regimen is considered to be acceptable.

Study Record Dates

• First Submitted: January 10, 2022
• First Posted: April 1, 2022
• Study Start: May 11, 2022
• Primary Completion: April 25, 2024
• Study Completion: April 25, 2025
• Last Updated: October 10, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)