Apatinib Versus Bevacizumab in Second-line Therapy for Colorectal Cancer(ABST-C)

Colorectal Neoplasms Clinical Trial

Official title: Apatinib Versus Bevacizumab in Combination With Second-line FOLFIRI in Patients With Metastatic Colorectal Cancer That Progressed During or After First-line Bevacizumab Plus an Oxaliplatin-based Regimen: A Randomised Phase 2 Trial

Status Recruiting

Clinical Trial Summary

Bevacizumab, as an antibody of vascular endothelial generated factor (VEGF), combined with the fluorouracil-based chemotherapy regimens for metastatic colorectal cancer, has become the classical first-line treatment. However, vast majority of patients eventually will suffer progression disease. The second-line treatment includes replacing chemotherapy regimens whistle continuing bevacizumab or other anti-VEGF antibodies, such as Aflibercept and Ramucirumab. Apatinib is a small molecule tyrosine kinase inhibitor (TKI), which can highly selectively bind to and strongly block VEGF receptor 2 (VEGFR - 2), also potently suppress the activities of Ret, c-kit and c-src, resulting in reduced cell migration, proliferation, and tumor microvascular density mediated by VEGF .There are already robust data showing that antibodies aimed at blocking VEGF signaling pathways combined with chemotherapy to treat advanced colorectal cancer is superior as compared to chemotherapy alone. Thus, we hypothesize that the effect of using the second-line chemotherapy regimens combined with apatinib may be superior to those combined with bevacizumab. In this study,the patients who have progressed following or on first-line oxaliplatin and 5-FU combined with bevacizumab are randomised into two arms. Patients in the experimental arm receive second-line FOLFIRI combined with apatinib and those in the control arm receive second-line FOLFIRI combined with bevacizumab. To compare the efficacy and safety of the two arms, progression-free survival(PFS) is the primary end point.If apatinib is superior to bevacizumab in the second-line setting,it is one possible option of anti-angiogenic therapy in combination with second-line FOLFIRI for treatment of advanced colorectal cancer.

Clinical Trial Description

Firstly, screen eligible mCRC patients for enrolment. Our CRC clinical nurse specialists will document medical history of patients including diagnoses, first-line chemotherapy (mFOLFOX6 or CAPOX),bevacizumab dosage,toxicities,PFS on previous therapy.In the meantime,chest-abdonimal-pelvic CT and blood tests are to be examined to assess base-line measurable lesions and guarantee adequate organ function prior to enrolment.If all the values meet the criteria for enrolment, consent will be signed.

Secondly, randomise patients into two arms: Arm A-apatinib plus FOLFIRI regimen and arm B-bevacizumab plus FOLFIRI regimen.A software which is alike the procedure of coin flipping is used to randomise eligible patients.According to the selected regimen in specific arm,patients will be given full-dose drugs or reduced dose drugs if serious toxicities ( CTCAE v4.0 criteria grade 3/4) are complained since previous cycle of treatment.Symptoms and blood test results (including CEA and CA199) before each cycle will be recorded and the consultant oncologist, who is responsible for individual participants, will decide whether to continue next cycle chemotherapy with apatinib or bevacizumab based on the assigned arm.Radiological assessment consisting of chest-abdonimal-pelvic CT will be performed every 2 months.Notably,the monitor will check with physicians and nurse specialists for the accuracy and completeness of all data.

Thirdly, follow up participants and analyse primary end point (PFS) and secondary end points (OS,ORR and DCR).The causes of confirmed missing data in the trial should be recorded in detail to determine the mechanism of missing data and choose the suitable missing data handling methods. ;

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Digestive System Neoplasms
• Gastrointestinal Neoplasms
• Intestinal Neoplasms
• Neoplasms

• NCT number: NCT03271255
• Study type: Interventional
• Source: Shenzhen People's Hospital
• Contact: Ruilian Xu, MD
• Phone: +8675522942497
• Email: xuruilian@126.com
• Status: Recruiting
• Phase: Phase 2
• Start date: May 23, 2018
• Completion date: December 31, 2022