Safety and Efficacy of Anlotinib in Combination With Irinotecan in Patients With Pretreated Advanced Colorectal Cancer
Primary Purpose
Colo-rectal Cancer
Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Anlotinib Hydrochloride with Irinotecan
Sponsored by
About this trial
This is an interventional treatment trial for Colo-rectal Cancer
Eligibility Criteria
Inclusion Criteria:
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
- willing and able to provide written informed consent and comply with the requirements of the study
- histologically- or cytologically-confirmed advanced colorectal cancer
- failed or intolerable to at least one prior therapy
- have evidence of measurable disease per RECIST v1.1
- Eastern Collaborative Oncology Group (ECOG) Performance Status ≤ 1
- weight ≥40kg
- life expectancy >12 weeks
Exclusion Criteria:
Subjects meeting any of the following criteria are ineligible for participation in the study:
- history of any anti-cancer therapy (including investigational agents) within 28 days prior to study entry
- presence of toxicity of prior anti-cancer therapy that has not resolved to Grade 1, as determined by National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03
- symptomatic brain metastasis requiring active treatment
- any previous malignancy, except for non squamous-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix within 5 years prior to study entry
- active or clinically unstable infection requiring systemic therapy
- unable to swallow oral medications or with gastrointestinal disorders that might interfere with proper absorption of oral drugs
- active digestive ulcer disease, inflammatory bowel disease, intestinal obstruction or any other condition that, in the clinical judgment of the Principal Investigator, may cause severe gastrointestinal bleeding or perforation
- unstable pulmonary embolism, deep vein thrombosis, or other significant arterial/venous thromboembolic event ≤2 months prior to study entry
- history of stroke or transient ischemic attack (TIA) within 12 months prior to study entry
any of the following abnormal findings in organ or marrow function 1 week prior to study entry:
- Leukocytes < 1.5*10^9/L, or Platelets < 100*10^9/L, or Hb< 90g/L
- Total bilirubin > 1.5 × institutional upper limit of normal (ULN), or AST (aspartate amino transferase)/ALT (alanine amino transferase)> 3 × institutional ULN for liver metastases, > 1.5 × institutional ULN in case of no liver metastases
- any electrolyte imbalance of clinical significance
- creatinine > institutional ULN and creatinine clearance < 60 mL/min
- spot urine protein ≥(2+) or 24-hour proteinuria ≥1.0g/24h
- APTT (activated partial thromboplastin time) or INR (international normalized ratio for prothrombin time) > 1.5 × institutional ULN
- treatment refractory hypertension defined as a blood pressure of systolic> 140 millimeter of mercury (mm Hg) and/or diastolic > 90 mm Hg which cannot be controlled by a single anti-hypertensive agent
- LVEF (left ventricular ejection fraction ) <50%
- history of acute coronary syndromes (including myocardial infarction and unstable angina), coronary artery bypass graft within 6 months prior to study entry, or history or evidence of current ≥ Class II congestive heart failure as defined by New York Heart Association (NYHA)
- present with non-healing fractures of bone or wounds of skin
- pregnant or lactating female
- sexually active female (of childbearing potential) or male unwilling to adopt an effective method of birth control during the course of the study
- serious and/or unstable pre-existing psychiatric disorder
- familial, sociological or geographical conditions that, in the clinical judgment of the Principal Investigator, do not permit compliance with the protocol
- known immediate or delayed hypersensitivity reaction to anlotinib, irinotecan or their excipients
- administration of irinotecan in prior treatments
Sites / Locations
- Jing HuangRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Anlotinib plus Irinotecan
Arm Description
Outcomes
Primary Outcome Measures
MTD
the maximum tolerated dose (MTD) of Anlotinib when administered in combination with fixed dose of irinotecan in advanced colorectal cancer patients.
ORR
the overall response rate (ORR) of Anlotinib when administered in combination with fixed dose of irinotecan in advanced colorectal cancer patients.
Secondary Outcome Measures
DCR
the disease control rate (DCR) of the combination of Anlotinib with Irinotecan in pretreated advanced colorectal cancer patients.
PFS
the progression free survival (PFS) of the combination of Anlotinib with Irinotecan in pretreated advanced colorectal cancer patients.
Full Information
NCT ID
NCT03545711
First Posted
May 23, 2018
Last Updated
August 3, 2018
Sponsor
Chinese Academy of Medical Sciences
1. Study Identification
Unique Protocol Identification Number
NCT03545711
Brief Title
Safety and Efficacy of Anlotinib in Combination With Irinotecan in Patients With Pretreated Advanced Colorectal Cancer
Official Title
Safety and Efficacy of Irinotecan Combined With Anlotinib in Patients With Pretreated Advanced Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Unknown status
Study Start Date
May 26, 2018 (Actual)
Primary Completion Date
November 24, 2019 (Anticipated)
Study Completion Date
November 24, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese Academy of Medical Sciences
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
Patients with pretreated advanced colorectal cancer are recruited to the phase I portion of this prospective non-randomised study in an escalated dose cohort. The primary endpoint of the dose-escalation phase is to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of anlotinib when given in combination with irinotecan. The phase II (dose-expansion) portion is designed to characterize the safety and potential efficacy of the combination therapy in pretreated advanced colorectal cancer patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colo-rectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Anlotinib plus Irinotecan
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Anlotinib Hydrochloride with Irinotecan
Intervention Description
Dose escalation of anlotinib starts from 8mg qd d1-14/q21d in combination with fixed dose of irinotecan at 180mg/m2 d1/q14d.
Primary Outcome Measure Information:
Title
MTD
Description
the maximum tolerated dose (MTD) of Anlotinib when administered in combination with fixed dose of irinotecan in advanced colorectal cancer patients.
Time Frame
6 months
Title
ORR
Description
the overall response rate (ORR) of Anlotinib when administered in combination with fixed dose of irinotecan in advanced colorectal cancer patients.
Time Frame
18 months
Secondary Outcome Measure Information:
Title
DCR
Description
the disease control rate (DCR) of the combination of Anlotinib with Irinotecan in pretreated advanced colorectal cancer patients.
Time Frame
18 months
Title
PFS
Description
the progression free survival (PFS) of the combination of Anlotinib with Irinotecan in pretreated advanced colorectal cancer patients.
Time Frame
18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
willing and able to provide written informed consent and comply with the requirements of the study
histologically- or cytologically-confirmed advanced colorectal cancer
failed or intolerable to at least one prior therapy
have evidence of measurable disease per RECIST v1.1
Eastern Collaborative Oncology Group (ECOG) Performance Status ≤ 1
weight ≥40kg
life expectancy >12 weeks
Exclusion Criteria:
Subjects meeting any of the following criteria are ineligible for participation in the study:
history of any anti-cancer therapy (including investigational agents) within 28 days prior to study entry
presence of toxicity of prior anti-cancer therapy that has not resolved to Grade 1, as determined by National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03
symptomatic brain metastasis requiring active treatment
any previous malignancy, except for non squamous-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix within 5 years prior to study entry
active or clinically unstable infection requiring systemic therapy
unable to swallow oral medications or with gastrointestinal disorders that might interfere with proper absorption of oral drugs
active digestive ulcer disease, inflammatory bowel disease, intestinal obstruction or any other condition that, in the clinical judgment of the Principal Investigator, may cause severe gastrointestinal bleeding or perforation
unstable pulmonary embolism, deep vein thrombosis, or other significant arterial/venous thromboembolic event ≤2 months prior to study entry
history of stroke or transient ischemic attack (TIA) within 12 months prior to study entry
any of the following abnormal findings in organ or marrow function 1 week prior to study entry:
Leukocytes < 1.5*10^9/L, or Platelets < 100*10^9/L, or Hb< 90g/L
Total bilirubin > 1.5 × institutional upper limit of normal (ULN), or AST (aspartate amino transferase)/ALT (alanine amino transferase)> 3 × institutional ULN for liver metastases, > 1.5 × institutional ULN in case of no liver metastases
any electrolyte imbalance of clinical significance
creatinine > institutional ULN and creatinine clearance < 60 mL/min
spot urine protein ≥(2+) or 24-hour proteinuria ≥1.0g/24h
APTT (activated partial thromboplastin time) or INR (international normalized ratio for prothrombin time) > 1.5 × institutional ULN
treatment refractory hypertension defined as a blood pressure of systolic> 140 millimeter of mercury (mm Hg) and/or diastolic > 90 mm Hg which cannot be controlled by a single anti-hypertensive agent
LVEF (left ventricular ejection fraction ) <50%
history of acute coronary syndromes (including myocardial infarction and unstable angina), coronary artery bypass graft within 6 months prior to study entry, or history or evidence of current ≥ Class II congestive heart failure as defined by New York Heart Association (NYHA)
present with non-healing fractures of bone or wounds of skin
pregnant or lactating female
sexually active female (of childbearing potential) or male unwilling to adopt an effective method of birth control during the course of the study
serious and/or unstable pre-existing psychiatric disorder
familial, sociological or geographical conditions that, in the clinical judgment of the Principal Investigator, do not permit compliance with the protocol
known immediate or delayed hypersensitivity reaction to anlotinib, irinotecan or their excipients
administration of irinotecan in prior treatments
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jing Huang, MD
Phone
86-10-87788102
Email
huangjingwg@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yan Song, M.D
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jing Huang, MD
Organizational Affiliation
Cancer Hospital,CAMS
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jing Huang
City
Beijing
ZIP/Postal Code
100021
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jing Huang, MD
12. IPD Sharing Statement
Plan to Share IPD
No
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Safety and Efficacy of Anlotinib in Combination With Irinotecan in Patients With Pretreated Advanced Colorectal Cancer
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