Apatinib in Refractory Colorectal Cancer

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

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.

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• Subjects who have withdrawn from standard treatment due to unacceptable toxicity and precluding retreatment with the same agent prior to progression of disease will also be allowed.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.