Neoadjuvant Therapy for Locally Advanced Rectal Cancer With Fruquintinib, Toripalimab and SRT

NCT05763927 | Unknown Phase 2

• 1 other identifier: 2021-013-CH11 IIT-CR
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the efficacy and safety of combined fruquintinib、toripalimab and SRT in neoadjuvant therapy for locally advanced rectal cancer.

Conditions

Rectal Cancer

Keywords

Fruquintinib; Toripalimab; SRT; neoadjuvant therapy; pCR

Outcome Measures

Primary Outcomes (1)

• pCR following neoadjuvant chemotherapy

  Pathologic complete response (pCR) rate defined as number of participants out of total that had no residual invasive disease (malignant cells)

  approximately 2 weeks after the resection of primary lesion

Secondary Outcomes (4)

• R0 resection rate

  approximately 2 weeks after the resection of primary lesion

• Objective response rate

  approximately before the resection of primary lesion

• 1 year DFS(disease free survival) rate

  1 year

• 1 year OS(overall survival) rate

  1 year

Study Arms (1)

Fruquintinib& Toripalimab& SRT

EXPERIMENTAL

Induction treatment: Fruquintinib 5mg d1-d14； Toripalimab 240 mg intravenously d1； Consolidation treatment: SRT: 25 Gy in 5 fractions d22-d26； Fruquitinib 5mg d22-d35，43-56,64-77； Toripalimab 240 mg intravenously d22、43、64； Surgery: Surgical resection will be performed according to the principles of TME(total mesorectal excision) 2-4 weeks after the last dose administration of Fruquintinib； Adjuvant chemotherapy: Standard chemotherapy or observation according to the judgement of Principle Investigator and patients' willing.

Drug: Fruquintinib; Drug: Toripalimab; Radiation: Short-course radiotherapy; Procedure: TME

Interventions

Fruquintinib DRUG

Fruquintinib 5mg 2w on/1w off, 21d/cycle, totally 4 cycle.

Fruquintinib& Toripalimab& SRT

Toripalimab DRUG

Toripalimab 200mg d1, 21d/cycle, totally 4 cycle.

Fruquintinib& Toripalimab& SRT

Short-course radiotherapy RADIATION

25 Gy in 5 fraction, d22-26.

Also known as: SRT

Fruquintinib& Toripalimab& SRT

TME PROCEDURE

Surgical resection of the primary tumour in the rectum, 2-4weeks after the last dose of fruquintinib

Also known as: Total mesorectal excision

Fruquintinib& Toripalimab& SRT

Eligibility Criteria

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

You may qualify if:

• Rectal adenocarcinoma was confirmed pathologically;
• Baseline clinical staging was T3-4 and/or N+, and rectal enhanced MRI was recommended as staging standard;
• distance from anus ≤12cm;
• No distant metastasis;
• Age 18-70, regardless of gender;
• ECOG(Eastern Cooperative Oncology Group) score ≤1;
• Major organ functions within 28 days prior to treatment meet the following criteria: A. Blood routine examination criteria (within 14 days without blood transfusion) : Hemoglobin (HB) ≥80g/L, absolute value of neutrophil (ANC) ≥1.5×109/L, absolute value of lymphocytes ≥ the lower limit of normal value, platelet (PLT) ≥80×109/L; B. Biochemical tests should meet the following criteria: Total bilirubin (TBIL) ≤1.5 times the upper limit of normal value (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; C. Coagulation tests should meet the following standards: International standardized ratio (INR) or prothrombin time (PT) ≤1.5 ULN; Activated partial thrombin time (APTT) ≤1.5 ULN (if the patient is on anticoagulant therapy, as long as PT and APTT are within the expected treatment range); D. Thyroid function: T3 and T4 levels were normal after drug treatment;
• No history of autoimmune diseases or current autoimmune diseases;
• Subjects must give informed consent to the study prior to the study and have voluntarily signed a written informed consent;
• The subjects can communicate well with the researcher and complete the study according to the protocol; Women of reproductive age ;
• should agree to use contraception (such as an intrauterine device, birth control pill or condom) during the study period and 120 days after the end of the study; Serum or urine pregnancy tests were negative during the 7 days prior to study enrollment.

You may not qualify if:

• Patients who have previously received immune checkpoint inhibitors;
• Known allergic reactions to PD-1 monoclonal antibody active ingredients, TKI inhibitor-related ingredients or any excipients;
• Patients with organ bleeding or bleeding tendency, except for rectal primary tumor bleeding (need investigator to assess the risk of bleeding;
• Pregnant or lactating women;
• years or at the same time have a history of other malignant tumors, but cured skin basal cell carcinoma and cervical carcinoma in situ and thyroid;
• Patients with uncontrolled epilepsy, central nervous system disease or mental disorders, the investigator judged that their clinical severity may hinder the signing of informed consent or affect the patient 's compliance with oral drugs;
• Clinically serious (i.e., active) heart disease, such as symptomatic coronary heart disease, New York Heart Association (NYHA) class II or more severe congestive heart failure or severe arrhythmia requiring drug intervention, or a history of myocardial infarction within the last 12 months;
• Subjects requiring systemic treatment with corticosteroids (greater than 10 mg prednisone equivalent daily) or other immunosuppressive agents (including organ transplant recipients) within 2 weeks before the first dose of study drug;
• Participated in other interventional drug clinical trials within 4 weeks before the first dose;
• Major surgery or severe trauma within 4 weeks before the first dose of study drug;
• Serious infection (CTCAE greater than grade 2) within 4 weeks before the first dose of study drug,Such as severe pneumonia, bacteremia, infectious complications requiring hospitalization; baseline chest imaging suggests active pulmonary inflammation, symptoms and signs of infection within 2 weeks before the first dose of study drug, or the need for oral or intravenous antibiotics (excluding prophylactic antibiotics);
• Active autoimmune diseases, history of autoimmune diseases (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases and syndromes); autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone, using stable doses of insulin type 1 diabetes can be included; but excluding vitiligo or recovered childhood asthma/allergy, without any intervention in adults;
• History of immunodeficiency, including positive HIV test, or other acquired, congenital immunodeficiency diseases, or history of organ transplantation and bone marrow transplantation;
• Active pulmonary tuberculosis infection found by medical history or CT examination, Or patients with a history of active pulmonary tuberculosis infection within 1 year before enrollment, or patients with a history of active pulmonary tuberculosis infection but without regular treatment 1 year before enrollment;
• Subjects with active hepatitis (HBV DNA ≥ 2000 IU/ml or 10000 copies/ml), hepatitis C (hepatitis C antibody positive,HCV-RNA was above the lower limit of detection of the assay);

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610000, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

HMPL-013; toripalimab

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

Study Officials

• Shared for: scientific research institutions, academic journal Shared for: scientific research institutions, academic journal, MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yaqin Zhao, MD

CONTACT

18628260828; zhaoyaqin@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Chief Physician

Study Record Dates

• First Submitted: February 27, 2023
• First Posted: March 10, 2023
• Study Start: September 1, 2022
• Primary Completion: October 1, 2024
• Study Completion: April 1, 2025
• Last Updated: March 10, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: Sharing period is 5 years, which start from one year after primary outcome publication.
• Access Criteria: Shared for: scientific research institutions, academic journal editors, government agencies Sharing conditions: IPD sharing shall meet the following conditions: Requestor must provide study agreement and relevant ethical review committee approval documents Requestor must ensure legality of data use and privacy protection Requestor must agree to data sharing, and the study team has the right to review the Requestor 's study plan and provide necessary support and interpretation of data

Locations

CN (1)