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

Primary Purpose

Rectal Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Fruquintinib
Toripalimab
Short-course radiotherapy
TME
Sponsored by
West China Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Cancer focused on measuring Fruquintinib, Toripalimab, SRT, neoadjuvant therapy, pCR

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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; No chemotherapy or other anti-tumor therapy was used before inclusion; 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. Exclusion Criteria: 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); Had a known history of psychotropic drug abuse, alcoholism, or drug use; 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.

Sites / Locations

  • West China Hospital, Sichuan UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fruquintinib& Toripalimab& SRT

Arm Description

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.

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

R0 resection rate
number of R0 surgery divide all participants (44pts)
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
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 OS(overall survival) rate
evaluate the 1-year OS rate after the neoadjuvant therapy

Full Information

First Posted
February 27, 2023
Last Updated
March 8, 2023
Sponsor
West China Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05763927
Brief Title
Neoadjuvant Therapy for Locally Advanced Rectal Cancer With Fruquintinib, Toripalimab and SRT
Official Title
Prospective Single-arm Phase II Clinical Study of Fruquintinib Combined With Toripalimab and SRT in Neoadjuvant Therapy for Locally Advanced Rectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2022 (Actual)
Primary Completion Date
October 1, 2024 (Anticipated)
Study Completion Date
April 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
West China Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer
Keywords
Fruquintinib, Toripalimab, SRT, neoadjuvant therapy, pCR

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Fruquintinib& Toripalimab& SRT
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Fruquintinib
Intervention Description
Fruquintinib 5mg 2w on/1w off, 21d/cycle, totally 4 cycle.
Intervention Type
Drug
Intervention Name(s)
Toripalimab
Intervention Description
Toripalimab 200mg d1, 21d/cycle, totally 4 cycle.
Intervention Type
Radiation
Intervention Name(s)
Short-course radiotherapy
Other Intervention Name(s)
SRT
Intervention Description
25 Gy in 5 fraction, d22-26.
Intervention Type
Procedure
Intervention Name(s)
TME
Other Intervention Name(s)
Total mesorectal excision
Intervention Description
Surgical resection of the primary tumour in the rectum, 2-4weeks after the last dose of fruquintinib
Primary Outcome Measure Information:
Title
pCR following neoadjuvant chemotherapy
Description
Pathologic complete response (pCR) rate defined as number of participants out of total that had no residual invasive disease (malignant cells)
Time Frame
approximately 2 weeks after the resection of primary lesion
Secondary Outcome Measure Information:
Title
R0 resection rate
Description
number of R0 surgery divide all participants (44pts)
Time Frame
approximately 2 weeks after the resection of primary lesion
Title
Objective response rate
Description
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
Time Frame
approximately before the resection of primary lesion
Title
1 year DFS(disease free survival) rate
Description
evaluate the 1-year DFS rate after the resection of primary lesion(only patients who acquire R0 resection)
Time Frame
1 year
Title
1 year OS(overall survival) rate
Description
evaluate the 1-year OS rate after the neoadjuvant therapy
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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; No chemotherapy or other anti-tumor therapy was used before inclusion; 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. Exclusion Criteria: 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); Had a known history of psychotropic drug abuse, alcoholism, or drug use; 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yaqin Zhao, MD
Phone
18628260828
Email
zhaoyaqin@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shared for: scientific research institutions, academic journal Shared for: scientific research institutions, academic journal, MD
Organizational Affiliation
West China Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
West China Hospital, Sichuan University
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhiping Li, MD
Phone
18980601784
Email
lizhliping620312@163.com

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

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

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