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

Prospective Single-arm Phase II Clinical Study of Fruquintinib Combined With Toripalimab and SRT in Neoadjuvant Therapy for Locally Advanced Rectal Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: Fruquintinib; Drug: Toripalimab; Radiation: Short-course radiotherapy; Procedure: TME

Detailed Description

The aim of this study is to investigate whether combined fruquintinib、toripalimab and SRT can achieve breakthrough efficacy in neoadjuvant therapy for locally advanced rectal cancer, achieving a better pCR rate and better tolerance compared with conventional neoadjuvant therapy for locally advanced rectal cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 44
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yaqin Zhao, MD; Phone Number: 18628260828; Email: zhaoyaqin@163.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Recruiting
      • West China Hospital, Sichuan University
      • Contact: Zhiping Li, MD; Phone Number: 18980601784; Email: lizhliping620312@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Rectal adenocarcinoma was confirmed pathologically;
2. Baseline clinical staging was T3-4 and/or N+, and rectal enhanced MRI was recommended as staging standard;
3. distance from anus ≤12cm;
4. No distant metastasis;
5. Age 18-70, regardless of gender;
6. ECOG(Eastern Cooperative Oncology Group) score ≤1;
7. No chemotherapy or other anti-tumor therapy was used before inclusion;
8. 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;
9. No history of autoimmune diseases or current autoimmune diseases;
10. Subjects must give informed consent to the study prior to the study and have voluntarily signed a written informed consent;
11. The subjects can communicate well with the researcher and complete the study according to the protocol; Women of reproductive age ;
12. 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.

Exclusion Criteria:

1. Patients who have previously received immune checkpoint inhibitors;
2. Known allergic reactions to PD-1 monoclonal antibody active ingredients, TKI inhibitor-related ingredients or any excipients;
3. Patients with organ bleeding or bleeding tendency, except for rectal primary tumor bleeding (need investigator to assess the risk of bleeding;
4. Pregnant or lactating women;
5. 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;
6. 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;
7. 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;
8. 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;
9. Participated in other interventional drug clinical trials within 4 weeks before the first dose;
10. Major surgery or severe trauma within 4 weeks before the first dose of study drug;
11. 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);
12. 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;
13. History of immunodeficiency, including positive HIV test, or other acquired, congenital immunodeficiency diseases, or history of organ transplantation and bone marrow transplantation;
14. 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;
15. 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);
16. Had a known history of psychotropic drug abuse, alcoholism, or drug use;
17. Had a history, illness, treatment, or laboratory abnormality that could interfere with the results of the trial, prevent the subject from participating throughout the study, or the investigator considered participation to be in the subject 's best interest.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Fruquintinib& Toripalimab& SRT; 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; Fruquintinib 5mg 2w on/1w off, 21d/cycle, totally 4 cycle.; Drug: Toripalimab; Toripalimab 200mg d1, 21d/cycle, totally 4 cycle.; Radiation: Short-course radiotherapy; 25 Gy in 5 fraction, d22-26.; Other Names: SRT; Procedure: TME; Surgical resection of the primary tumour in the rectum, 2-4weeks after the last dose of fruquintinib; Other Names: Total mesorectal excision

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	number of R0 surgery divide all participants (44pts)	approximately 2 weeks after the resection of primary lesion
Objective response rate	Objective tumour response (ORR) will is defined as the proportion of subjects who achieve a partial or complete response according to RECIST criteria version 1.1	approximately before the resection of primary lesion
1 year DFS(disease free survival) rate	evaluate the 1-year DFS rate after the resection of primary lesion（only patients who acquire R0 resection）	1 year
1 year OS(overall survival) rate	evaluate the 1-year OS rate after the neoadjuvant therapy	1 year

Collaborators and Investigators

• Sponsor: West China Hospital
• Investigators: Principal Investigator: Shared for: scientific research institutions, academic journal Shared for: scientific research institutions, academic journal, MD, West China Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: February 27, 2023
• First Submitted That Met QC Criteria: March 8, 2023
• First Posted (Estimate): March 10, 2023

Study Record Updates

• Last Update Posted (Estimate): March 10, 2023
• Last Update Submitted That Met QC Criteria: March 8, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: neoadjuvant therapy; Toripalimab; pCR; Fruquintinib; SRT
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: 2021-013-CH11 IIT-CR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

IPD(individual patient data) Sharing Plan:

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

Scope of shared data: The shared data includes ECG and clinical data of all subjects, but excluding personal information of subjects

• IPD Sharing Time Frame: Sharing period is 5 years, which start from one year after primary outcome publication.
• IPD Sharing 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No