Apatinib in Refractory Colorectal Cancer

Study Overview
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Brief Summary
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Limited agents have been approved after standard first and second line treatment. Regorafenib and Trifluridine/Tipiracil (TAS-102) are still not approved in China.Apatinib has shown significant efficacy in refractory advanced gastric cancer regarding PFS and OS with controllable toxicity.This study is aimed to explore the efficacy,safety as well as predictive biomarker in advanced colorectal cancer failed to standard therapy in Chinese population.

Official Title
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A Single Arm, Open Label, Multicenter Exploratory Study of Apatinib in Patients With Metastatic Colorectal Cancer (CRC) Who Have Progressed After Standard Second Line Therapy

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Drug: apatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded. Subjects with metastatic colorectal cancer(CRC) (Stage IV). Subjects must have failed at least two lines of prior treatment, which must include a fluoropyrimidine, oxaliplatin and irinotecan. Subjects treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy. Subjects who have withdrawn from standard treatment due to unacceptable toxicity and precluding retreatment with the same agent prior to progression of disease will also be allowed. Prior treatment with bevacizumab and/or cetuximab will be allowed. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1.is necessary. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. Life expectancy of at least 3 months. Adequate bone marrow, liver and renal function as assessed by the laboratory required by protocol. assigned informed consent. Exclusion Criteria: Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)]. Participants of other clinical trial within 4 weeks. Diseases which will impact the absorption of apatinib, eg. dysphagia, chronic diarrhea, bowl obstruction Hemorrhage events of ≥grade 3 within 4 weeks. known central nervous system metastasis. Uncontrolled hypertension. (Systolic blood pressure 140 mmHg or diastolic pressure 90 mmHg despite optimal medical management). Unstable angina,congestive heart failure,Myocardial infarction, Cardiac arrhythmias requiring anti-arrhythmic therapy. urine protein ≥++ and 24h urine protein more than 1.0g. Chronically green wound or bone fracture. Arterial or venous thrombotic or embolic events. Tumor invading important blood vessel with high risk of severe hemorrhage. Abnormal coagulation function. thromboemboli events within 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: drug,apatinib<br>apatinib 500mg/qd, 28d/cycle | Drug: apatinib<br>* apatinib 500mg/qd, 28d/cycle<br>* Other names: YN968D1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival(PFS) | PFS was defined as the time from assignment to disease progression radiological/clinical or death due to any cause, whichever occurs first. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation. | From assignment of the first subject to 3 months later after the last participant is recruited.The last participant will be recruited before Mar 30,2019 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from date of assignment to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact. | From assignment of the first subject until 40 death events observed, up to 2 years. | 
| Disease control rate (DCR) | DCR is defined as the percentage of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD) | From assignment of the first subject to 3 months later after the last participant is recruited.The last participant will be recruited before Mar 30,2019 | 
| Objective response rate(ORR) | The percentage of subjects with total number of Complete Response (CR) + total number of Partial Response (PR) | From assignment of the first subject to 3 months later after the last participant is recruited.The last participant will be recruited before Mar 30,2019 | 
| Quality of life | The general well-being of participants, outlining negative and positive features of life. | From assignment of the first subject to 3 months later after the last participant is recruited.The last participant will be recruited before Mar 30,2019 | 
| relationship between the tumor molecular burden & gene mutation and the drug efficacy. | The tumor molecular clones and gene mutations of 1021 tumor related genes will be detected by next-generation sequencing,which will be matched with the CT scanning . | From assignment of the first subject to 3 months later after the last participant is recruited.The last participant will be recruited before Mar 30,2019. | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | adverse events will be assessed according to CTCAE v4.0, including hematological and non-hematological adverse events. Non-hematological adverse events will be collected by patients reported outcomes questionaire. The adverse events of interest include hypertension,hand-foot syndrome,proteinuria,hoarseness,rash,etc.The dose reduction and drug discontinuance due to adverse events will also be recorded. | From assignment of the first subject to 3 months later after the last participant is recruited.The last participant will be recruited before Mar 30,2019. |