Back to resultsA Phase II/III Study of HR070803 in Combination With Oxaliplatin, 5-fluorouracil, Calcium Folinate and Bevacizumab Versus FOLFOX in Combination With Bevacizumab for First-line Treatment of Advanced Colorectal Cancer
Primary Purpose
Colorectal Cancer
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
HR070803 plus oxaliplatin, 5-FU/LV, bevacizumab
HR070803 simulator plus oxaliplatin, 5-FU/LV, bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
Eligibility Criteria
Inclusion Criteria: Male or female who is 18-75 years of age; Histologically-confirmed metastatic and unresectable (Stage IV as defined by American Joint Committee on Cancer [AJCC eighth edition]) colorectal adenocarcinoma No previous systemic antitumor therapy (including but not limited to systemic chemotherapy, molecularly targeted therapy, immunotherapy, biotherapy, and other investigational therapeutic agents) for colorectal cancer (patients with confirmed relapse ≥6 months after the last administration of neoadjuvant or adjuvant therapy can be enrolled); Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 ; Life expectancy of ≥ 6 months; Vital organ functions meet the criteria. Exclusion Criteria: With confirmed MMR deficient (dMMR) or microsatellite instability high (MSI-H). With central nervous system metastases. Previous oxaliplatin-containing chemotherapy within 12 months prior to enrolment. Previous treatment with irinotecan, immune checkpoint inhibitor, anti-epidermal growth factor receptor or any anti-angiogenic drug. Patients with large amount of pleural effusion, ascites or pericardial effusion that could not reach a stable state within 2 weeks prior to enrolment. Severe gastrointestinal dysfunction (inflammation or diarrhea > grade 1). With diagnosed interstitial lung disease. Severe cardiovascular and cerebrovascular diseases. Peripheral neuropathy > grade 1. Intestinal obstruction within the 6 months prior to enrolment. Gastrointestinal perforation, gastrointestinal fistula, intraperitoneal abscess, and non-gastrointestinal fistula (e.g. tracheoesophageal fistula) within 6 months prior to enrolment. Patients with CTCAE≥ grade 3 gastrointestinal bleeding within 6 months prior to enrolment, or any grade gastrointestinal bleeding within 1 month prior to enrolment. Patients with CTCAE≥ grade 3 extra-gastrointestinal bleeding within 6 months prior to enrolment, or CTCAE≥ grade 2 extra-gastrointestinal bleeding within 3 months prior to enrolment. Uncontrolled hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg under regular antihypertensive therapy), and a history of hypertensive crisis or hypertensive encephalopathy. History of hypersensitivity or contraindications to any of irinotecan liposomes/simulator, irinotecan, other liposomal products, 5-FU, calcium folinate, oxaliplatin, bevacizumab.
Sites / Locations
- Sun Yat-Sen University Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
HR070803
HR070803 simulator
Arm Description
HR070803 plus oxaliplatin, 5-FU/LV, bevacizumab
HR070803 simulator plus oxaliplatin, 5-FU/LV, bevacizumab
Outcomes
Primary Outcome Measures
Adverse Events (AE) According to NCI-CTCAE v5.0（Phase II）
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant after signing the informed consent form and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that is temporally associated with the use of study treatment, is also an AE.
Serious Adverse Events (SAE)（Phase II）
An SAE is defined as any of the following adverse events in a participant or clinical investigation participant after signing the informed consent form and which does not necessarily have to have a causal relationship with this treatment: events that result in death, life-threatening events; events requiring hospitalization or prolonged hospitalization; events leading to permanent or severe disability/loss of function (significant impairment of the ability to carry out normal life functions); congenital abnormalities or birth defects; a medically important event or intervention may be required to prevent any of these outcomes.
Progression-Free Survival (PFS) Assessed by IRC（Phase III）
from randomization to PD or death from any cause
Secondary Outcome Measures
Overall Response Rate (ORR) Assessed by investigator（Phase II）
The proportion of patients who acquired complete response and partial response during treatment.
Disease Control Rate (DCR) by investigator（Phase II）
The proportion of patients who acquired complete response and partial response and stable disease during treatment.
Duration of Overall Response (DoR) by investigator（Phase II）
For subjects who demonstrated CR or PR, response duration is defined as the time from the date of first response (CR or PR) until the date of first documented disease progression or death.
Progression-Free Survival (PFS) Assessed by investigator（Phase II）
from randomization to PD or death from any cause.
Overall Survival (OS)（Phase II）
from randomization to death from any cause.
Characterize the PK（Phase II）
Serum concentrations of SN-38 and CPT-11 will be monitored. PK modeling will be performed and an appropriate model will be selected to describe the data.
Overall Survival (OS)（Phase III）
from randomization to death from any cause.
Progression-Free Survival (PFS) Assessed by investigator（Phase III）
from randomization to PD or death from any cause.
Overall Response Rate (ORR) Assessed by IRC and investigator（Phase III）
The proportion of patients who acquired complete response and partial response during treatment.
Duration of Overall Response (DoR) by IRC and investigator（Phase III）
For subjects who demonstrated CR or PR, response duration is defined as the time from the date of first response (CR or PR) until the date of first documented disease progression or death.
Disease Control Rate（DCR） by IRC and investigator（Phase III）
The proportion of patients who acquired complete response and partial response and stable disease during treatment.
Adverse Events (AE) According to NCI-CTCAE v5.0（Phase III）
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant after signing the informed consent form and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that is temporally associated with the use of study treatment, is also an AE.
Serious Adverse Events (SAE)（Phase III）
An SAE is defined as any of the following adverse events in a participant or clinical investigation participant after signing the informed consent form and which does not necessarily have to have a causal relationship with this treatment: events that result in death; life-threatening events; events requiring hospitalization or prolonged hospitalization; events leading to permanent or severe disability/loss of function (significant impairment of the ability to carry out normal life functions); congenital abnormalities or birth defects; a medically important event or intervention may be required to prevent any of these outcomes.
Full Information
NCT ID
NCT05945901
First Posted
July 7, 2023
Last Updated
August 22, 2023
Sponsor
Jiangsu HengRui Medicine Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05945901
Brief Title
A Phase II/III Study of HR070803 in Combination With Oxaliplatin, 5-fluorouracil, Calcium Folinate and Bevacizumab Versus FOLFOX in Combination With Bevacizumab for First-line Treatment of Advanced Colorectal Cancer
Official Title
A Phase II/III, Double-blind, Randomized, Multi-center Study of HR070803 in Combination With Oxaliplatin, 5-fluorouracil, Calcium Folinate and Bevacizumab Versus FOLFOX in Combination With Bevacizumab for First-line Treatment of Advanced Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 14, 2023 (Actual)
Primary Completion Date
December 1, 2025 (Anticipated)
Study Completion Date
December 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jiangsu HengRui Medicine Co., Ltd.
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
This is a double-blind, randomized, multi-center, II/III study in at least 606 patients with advanced colorectal cancer. The study is being conducted to evaluate the safety of HR070803 combined with oxaliplatin, 5-FU/LV and bevacizumab in phase II and to evaluate the efficacy of HR070803 in combination with oxaliplatin, 5-FU/LV, and bevacizumab versus HR070803 simulator in combination with FOLFOX and bevacizumab for first-line treatment of patients with unresectable metastatic colorectal cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
606 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
HR070803
Arm Type
Experimental
Arm Description
HR070803 plus oxaliplatin, 5-FU/LV, bevacizumab
Arm Title
HR070803 simulator
Arm Type
Placebo Comparator
Arm Description
HR070803 simulator plus oxaliplatin, 5-FU/LV, bevacizumab
Intervention Type
Drug
Intervention Name(s)
HR070803 plus oxaliplatin, 5-FU/LV, bevacizumab
Intervention Description
HR070803 plus oxaliplatin, 5-FU/LV, bevacizumab Patients will receive the study drug after randomization, and those with effective efficacy evaluation (CR, PR or SD) will receive intravenous chemotherapy for up to 8-12 cycles, and then enter the maintenance treatment stage until PD, death, intolerable toxicity or withdrawal of informed consent (whichever occurs first)
Intervention Type
Drug
Intervention Name(s)
HR070803 simulator plus oxaliplatin, 5-FU/LV, bevacizumab
Intervention Description
HR070803 simulator plus oxaliplatin, 5-FU/LV, bevacizumab Patients will receive the study drug after randomization, and those with effective efficacy evaluation (CR, PR or SD) will receive intravenous chemotherapy for up to 8-12 cycles, and then enter the maintenance treatment stage until PD, death, intolerable toxicity or withdrawal of informed consent (whichever occurs first)
Primary Outcome Measure Information:
Title
Adverse Events (AE) According to NCI-CTCAE v5.0（Phase II）
Description
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant after signing the informed consent form and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that is temporally associated with the use of study treatment, is also an AE.
Time Frame
From Baseline to primary completion date, about 48 months
Title
Serious Adverse Events (SAE)（Phase II）
Description
An SAE is defined as any of the following adverse events in a participant or clinical investigation participant after signing the informed consent form and which does not necessarily have to have a causal relationship with this treatment: events that result in death, life-threatening events; events requiring hospitalization or prolonged hospitalization; events leading to permanent or severe disability/loss of function (significant impairment of the ability to carry out normal life functions); congenital abnormalities or birth defects; a medically important event or intervention may be required to prevent any of these outcomes.
Time Frame
From Baseline to primary completion date, about 48 months
Title
Progression-Free Survival (PFS) Assessed by IRC（Phase III）
Description
from randomization to PD or death from any cause
Time Frame
From Baseline to primary completion date, about 48 months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR) Assessed by investigator（Phase II）
Description
The proportion of patients who acquired complete response and partial response during treatment.
Time Frame
From Baseline to primary completion date, about 48 months
Title
Disease Control Rate (DCR) by investigator（Phase II）
Description
The proportion of patients who acquired complete response and partial response and stable disease during treatment.
Time Frame
From Baseline to primary completion date, about 48 months
Title
Duration of Overall Response (DoR) by investigator（Phase II）
Description
For subjects who demonstrated CR or PR, response duration is defined as the time from the date of first response (CR or PR) until the date of first documented disease progression or death.
Time Frame
From Baseline to primary completion date, about 48 months
Title
Progression-Free Survival (PFS) Assessed by investigator（Phase II）
Description
from randomization to PD or death from any cause.
Time Frame
From Baseline to primary completion date, about 48 months
Title
Overall Survival (OS)（Phase II）
Description
from randomization to death from any cause.
Time Frame
From Baseline to primary completion date, about 48 months
Title
Characterize the PK（Phase II）
Description
Serum concentrations of SN-38 and CPT-11 will be monitored. PK modeling will be performed and an appropriate model will be selected to describe the data.
Time Frame
From Baseline to primary completion date, about 48 months
Title
Overall Survival (OS)（Phase III）
Description
from randomization to death from any cause.
Time Frame
From Baseline to primary completion date, about 48 months
Title
Progression-Free Survival (PFS) Assessed by investigator（Phase III）
Description
from randomization to PD or death from any cause.
Time Frame
From Baseline to primary completion date, about 48 months
Title
Overall Response Rate (ORR) Assessed by IRC and investigator（Phase III）
Description
The proportion of patients who acquired complete response and partial response during treatment.
Time Frame
From Baseline to primary completion date, about 48 months
Title
Duration of Overall Response (DoR) by IRC and investigator（Phase III）
Description
For subjects who demonstrated CR or PR, response duration is defined as the time from the date of first response (CR or PR) until the date of first documented disease progression or death.
Time Frame
From Baseline to primary completion date, about 48 months
Title
Disease Control Rate（DCR） by IRC and investigator（Phase III）
Description
The proportion of patients who acquired complete response and partial response and stable disease during treatment.
Time Frame
From Baseline to primary completion date, about 48 months
Title
Adverse Events (AE) According to NCI-CTCAE v5.0（Phase III）
Description
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant after signing the informed consent form and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that is temporally associated with the use of study treatment, is also an AE.
Time Frame
From Baseline to primary completion date, about 48 months
Title
Serious Adverse Events (SAE)（Phase III）
Description
An SAE is defined as any of the following adverse events in a participant or clinical investigation participant after signing the informed consent form and which does not necessarily have to have a causal relationship with this treatment: events that result in death; life-threatening events; events requiring hospitalization or prolonged hospitalization; events leading to permanent or severe disability/loss of function (significant impairment of the ability to carry out normal life functions); congenital abnormalities or birth defects; a medically important event or intervention may be required to prevent any of these outcomes.
Time Frame
From Baseline to primary completion date, about 48 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:
Male or female who is 18-75 years of age;
Histologically-confirmed metastatic and unresectable (Stage IV as defined by American Joint Committee on Cancer [AJCC eighth edition]) colorectal adenocarcinoma
No previous systemic antitumor therapy (including but not limited to systemic chemotherapy, molecularly targeted therapy, immunotherapy, biotherapy, and other investigational therapeutic agents) for colorectal cancer (patients with confirmed relapse ≥6 months after the last administration of neoadjuvant or adjuvant therapy can be enrolled);
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 ;
Life expectancy of ≥ 6 months;
Vital organ functions meet the criteria.
Exclusion Criteria:
With confirmed MMR deficient (dMMR) or microsatellite instability high (MSI-H).
With central nervous system metastases.
Previous oxaliplatin-containing chemotherapy within 12 months prior to enrolment.
Previous treatment with irinotecan, immune checkpoint inhibitor, anti-epidermal growth factor receptor or any anti-angiogenic drug.
Patients with large amount of pleural effusion, ascites or pericardial effusion that could not reach a stable state within 2 weeks prior to enrolment.
Severe gastrointestinal dysfunction (inflammation or diarrhea > grade 1).
With diagnosed interstitial lung disease.
Severe cardiovascular and cerebrovascular diseases.
Peripheral neuropathy > grade 1.
Intestinal obstruction within the 6 months prior to enrolment.
Gastrointestinal perforation, gastrointestinal fistula, intraperitoneal abscess, and non-gastrointestinal fistula (e.g. tracheoesophageal fistula) within 6 months prior to enrolment.
Patients with CTCAE≥ grade 3 gastrointestinal bleeding within 6 months prior to enrolment, or any grade gastrointestinal bleeding within 1 month prior to enrolment.
Patients with CTCAE≥ grade 3 extra-gastrointestinal bleeding within 6 months prior to enrolment, or CTCAE≥ grade 2 extra-gastrointestinal bleeding within 3 months prior to enrolment.
Uncontrolled hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg under regular antihypertensive therapy), and a history of hypertensive crisis or hypertensive encephalopathy.
History of hypersensitivity or contraindications to any of irinotecan liposomes/simulator, irinotecan, other liposomal products, 5-FU, calcium folinate, oxaliplatin, bevacizumab.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yuezheng Ti
Phone
+0518-82342973
Email
yuezheng.ti@hengrui.com
Facility Information:
Facility Name
Sun Yat-Sen University Cancer Center
City
Guangzhou
State/Province
Guangdog
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ruihua Xu
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
A Phase II/III Study of HR070803 in Combination With Oxaliplatin, 5-fluorouracil, Calcium Folinate and Bevacizumab Versus FOLFOX in Combination With Bevacizumab for First-line Treatment of Advanced Colorectal Cancer
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