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Envafolimab Combined With Trifluridine/Tipiracil and Bevacizumab in the Treatment of Refractory mCRC.

Primary Purpose

Metastatic Colorectal Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Envafolimab
Trifluridine/Tipiracil
Bevacizumab
Sponsored by
The First Affiliated Hospital with Nanjing Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer

Eligibility Criteria

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

Inclusion Criteria: Patient able and willing to provide written informed consent and to comply with the study protocol and follow-up inspection. Histologically or cytologically documented diagnosis of metastatic colorectal cancer refractory to second-line and above standard treatment; presence of at least one measurable lesions which should be measured on CT or MRI following RECIST 1.1 criteria. ECOG (Eastern Cooperative Oncology Group) performance status 0-2. Life expectancy of at least 3 months. Patient had no serious hematologic,hepatic, or renal abnormalities, and the results within a week were consistent with the following laboratory tests: Hematological Parameters: Neutrophil count ≥1.5×109/L;Platelets ≥80×109/L;Hemoglobin≥90g/L. Hepatic Function Parameters: AST and ALT ≤2.5×upper limit of normal(≤5×ULN if liver metastasis present); Bilirubin ≤2.5 ×upper limit of normal. Renal Function Parameters: Cr ≤ 1.5×upper limit of normal. Coagulation Function Parameters: International Normalized Ratio (INR)≤1.5 or prothrombin time (PT)≤1.5×ULN or activated partial prothrombin time (APTT)≤1.5×ULN. Urinary protein≤1+, 24-hour urinary protein quantity ≤1.0g. Exclusion Criteria: Symptomatic or known central nervous system metastases (head CT or MRI is not required to rule out brain metastases). For patients with suspected neurological metastasis, head CT or MRI should be performed within 28 days before enrollment to rule out neurological metastasis. The target lesion was treated locally within 3 months. There are neurological or psychiatric abnormalities that affect cognitive ability. Subjects with hypertension not well controlled by single antihypertensive medication (systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg); Patients with history of unstable angina pectoris; Patients with newly diagnosed angina pectoris or myocardial infarction within 3 months prior to screening; Arrhythmias (including QTcF: ≥450 ms in men and ≥470 ms inwomen) require long-term use of antiarrhythmic drugs and New York Heart Association grade ≥II cardiac insufficiency. Prior or combined history of other malignancies, with the exception of cured basal cell carcinoma of the skin,carcinoma in situ of the cervix, and other early tumors that are expected to be free of recurrence within six months after radical treatment. Patients currently receiving or having received anticancer therapies within 4 weeks prior to the enrollment. For female subjects: should be surgically sterilized, postmenopausal, or consent to use a medically approved contraceptive during the study treatment and for 6 months after the end of the study treatment period; Serum or urine pregnancy tests must be negative within 7days prior to study enrollment and must be non-lactating. Male subjects: Patients who should be surgically sterilized or who have consented to use a medically approved contraceptive method during the study treatment period and for 6 months after the end of the study treatment period. There are multiple factors that affect oral medications (such as inability to swallow,chronic diarrhea, and intestinal obstruction). Patients with active bleeding, long-term unhealed wounds, and any surgical procedures within 2 months. Any arteriovenous thrombosis event occurred within 6 months, including cerebrovascular accident, deep vein thrombosis (deep vein thrombosis caused by the installation of a deep vein catheter in the previous chemotherapy, except for those who were judged to have recovered by the investigator), and pulmonary embolism. Severe chest and abdominal fluid, requiring clinical intervention. Have thyroid dysfunction that cannot be maintained within the normal range despite medication. History of immune deficiency or organ transplantation. There were other concomitant diseases that the investigators determined to seriously endanger the patient's safety or interfere with the patient's completion of the study.

Sites / Locations

  • The First Affiliated Hospital with Nanjing Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

triplet combination therapy

Arm Description

Envafolimab Combined With Trifluridine/Tipiracil and Bevacizumab

Outcomes

Primary Outcome Measures

ORR(Objective response rate)
Objective Response Rate defined as the proportion of patients with objective evidence of complete response (CR) or partial response (PR) according to RECIST version 1.1 criteria and using investigator's tumor assessment.

Secondary Outcome Measures

OS (Overall Survival)
Overall survival defined as the observed time elapsed between the date of first treatment and the date of death due to any cause.
PFS (Progression-free survival)
Progression-free survival defined as the time elapsed between the randomization and the date of radiologic tumour progression according to RECIST version 1.1 by investigator's judgement or death from any cause, whichever comes first.
DCR (Disease control rate)
Disease control rate defined as the proportion of patients with objective evidence of CR or PR or stable disease (SD) according to RECIST version 1.1 criteria and using investigator's tumor assessment.
Quality of life: EORTC QLQ-C30
Assess patients health and activities using the European Organization for Research and Treatment of Cancer Core Quality of Life (EORTC QLQ-C30) module.

Full Information

First Posted
September 24, 2023
Last Updated
October 10, 2023
Sponsor
The First Affiliated Hospital with Nanjing Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT06060704
Brief Title
Envafolimab Combined With Trifluridine/Tipiracil and Bevacizumab in the Treatment of Refractory mCRC.
Official Title
A Prospective, Open, Single-center, Single-arm Study to Explore Envafolimab Combined With Trifluridine/Tipiracil and Bevacizumab in the Treatment of mCRC Patients Who Were Refractory to Second-line and Above Standard Therapy.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
September 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Affiliated Hospital with Nanjing Medical University

4. Oversight

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

5. Study Description

Brief Summary
The goal of this single-arm study is to evaluate the efficacy and safety of Envafolimab combined with Trifluridine/Tipiracil and Bevacizumab in the treatment of metastatic colorectal cancer patients who are refractory or intolerant to standard therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Envafolimab Combined With Trifluridine/Tipiracil and Bevacizumab
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
triplet combination therapy
Arm Type
Experimental
Arm Description
Envafolimab Combined With Trifluridine/Tipiracil and Bevacizumab
Intervention Type
Drug
Intervention Name(s)
Envafolimab
Intervention Description
150mg Qw, delivered as a single 1.5ml subcutaneous injection in under 30s , every 4 weeks for one cycle(Q4w).
Intervention Type
Drug
Intervention Name(s)
Trifluridine/Tipiracil
Other Intervention Name(s)
TAS-102, FTD/TPI
Intervention Description
35 mg/m2 (maximum single dose of 80 mg), po, on days 1-5 and 8-12 of each treatment cycle, twice daily for 28 days, within 1 hour after breakfast or dinner take medicine.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Intervention Description
ivgtt, 5mg/kg, d1, d15, every 4 weeks for one cycle (Q4w). The subjects will receive Trifluridine/Tipiracil plus Bevacizumab and Envafolimab until disease progression, intolerable toxicity, initiation of other anti-tumor therapy, death, withdrawal of informed consent, or loss of follow-up.
Primary Outcome Measure Information:
Title
ORR(Objective response rate)
Description
Objective Response Rate defined as the proportion of patients with objective evidence of complete response (CR) or partial response (PR) according to RECIST version 1.1 criteria and using investigator's tumor assessment.
Time Frame
Approximately 12 months
Secondary Outcome Measure Information:
Title
OS (Overall Survival)
Description
Overall survival defined as the observed time elapsed between the date of first treatment and the date of death due to any cause.
Time Frame
Approximately 12 months
Title
PFS (Progression-free survival)
Description
Progression-free survival defined as the time elapsed between the randomization and the date of radiologic tumour progression according to RECIST version 1.1 by investigator's judgement or death from any cause, whichever comes first.
Time Frame
Approximately 12 months
Title
DCR (Disease control rate)
Description
Disease control rate defined as the proportion of patients with objective evidence of CR or PR or stable disease (SD) according to RECIST version 1.1 criteria and using investigator's tumor assessment.
Time Frame
Approximately 12 months
Title
Quality of life: EORTC QLQ-C30
Description
Assess patients health and activities using the European Organization for Research and Treatment of Cancer Core Quality of Life (EORTC QLQ-C30) module.
Time Frame
Approximately 12 months

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: Patient able and willing to provide written informed consent and to comply with the study protocol and follow-up inspection. Histologically or cytologically documented diagnosis of metastatic colorectal cancer refractory to second-line and above standard treatment; presence of at least one measurable lesions which should be measured on CT or MRI following RECIST 1.1 criteria. ECOG (Eastern Cooperative Oncology Group) performance status 0-2. Life expectancy of at least 3 months. Patient had no serious hematologic,hepatic, or renal abnormalities, and the results within a week were consistent with the following laboratory tests: Hematological Parameters: Neutrophil count ≥1.5×109/L;Platelets ≥80×109/L;Hemoglobin≥90g/L. Hepatic Function Parameters: AST and ALT ≤2.5×upper limit of normal(≤5×ULN if liver metastasis present); Bilirubin ≤2.5 ×upper limit of normal. Renal Function Parameters: Cr ≤ 1.5×upper limit of normal. Coagulation Function Parameters: International Normalized Ratio (INR)≤1.5 or prothrombin time (PT)≤1.5×ULN or activated partial prothrombin time (APTT)≤1.5×ULN. Urinary protein≤1+, 24-hour urinary protein quantity ≤1.0g. Exclusion Criteria: Symptomatic or known central nervous system metastases (head CT or MRI is not required to rule out brain metastases). For patients with suspected neurological metastasis, head CT or MRI should be performed within 28 days before enrollment to rule out neurological metastasis. The target lesion was treated locally within 3 months. There are neurological or psychiatric abnormalities that affect cognitive ability. Subjects with hypertension not well controlled by single antihypertensive medication (systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg); Patients with history of unstable angina pectoris; Patients with newly diagnosed angina pectoris or myocardial infarction within 3 months prior to screening; Arrhythmias (including QTcF: ≥450 ms in men and ≥470 ms inwomen) require long-term use of antiarrhythmic drugs and New York Heart Association grade ≥II cardiac insufficiency. Prior or combined history of other malignancies, with the exception of cured basal cell carcinoma of the skin,carcinoma in situ of the cervix, and other early tumors that are expected to be free of recurrence within six months after radical treatment. Patients currently receiving or having received anticancer therapies within 4 weeks prior to the enrollment. For female subjects: should be surgically sterilized, postmenopausal, or consent to use a medically approved contraceptive during the study treatment and for 6 months after the end of the study treatment period; Serum or urine pregnancy tests must be negative within 7days prior to study enrollment and must be non-lactating. Male subjects: Patients who should be surgically sterilized or who have consented to use a medically approved contraceptive method during the study treatment period and for 6 months after the end of the study treatment period. There are multiple factors that affect oral medications (such as inability to swallow,chronic diarrhea, and intestinal obstruction). Patients with active bleeding, long-term unhealed wounds, and any surgical procedures within 2 months. Any arteriovenous thrombosis event occurred within 6 months, including cerebrovascular accident, deep vein thrombosis (deep vein thrombosis caused by the installation of a deep vein catheter in the previous chemotherapy, except for those who were judged to have recovered by the investigator), and pulmonary embolism. Severe chest and abdominal fluid, requiring clinical intervention. Have thyroid dysfunction that cannot be maintained within the normal range despite medication. History of immune deficiency or organ transplantation. There were other concomitant diseases that the investigators determined to seriously endanger the patient's safety or interfere with the patient's completion of the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yanhong Gu, ph.d
Phone
+86 13813908678
Email
guluer@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Tianzhu Qiu
Phone
+86 18013873919
Email
tianzhu_qiu@n.jmu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yanhong Gu
Organizational Affiliation
The First Affiliated Hospital with Nanjing Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital with Nanjing Medical University
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210029
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yanhong Gu, Ph.D
Phone
+86 13813908678
Email
guluer@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Envafolimab Combined With Trifluridine/Tipiracil and Bevacizumab in the Treatment of Refractory mCRC.

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