Apatinib Treatment as the Neoadjuvant Therapy in Advanced Colorectal Cancer

A Real World Study of Efficacy and Safety for Apatinib Treatment as the Neoadjuvant Therapy in Advanced Colorectal Cancer

Apatinib has been proved to be effective and safe among patients in advanced colorectal cancer in several trials. the investigators aimed to evaluate its efficacy and safety as the neoadjuvant therapy in real world practice, and to explore factors associated with efficacy.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer; Neoadjuvant Therapy
• Intervention / Treatment: Drug: FOLFOX regimen; Drug: apatinib and FOLFOX regimen

Detailed Description

Regorafenib (BAY 73-4506, commercial name Stivarga) is an oral multi-kinase inhibitor developed by Bayer which shows anti-angiogenic activity due to its dual targeted VEGFR2-TIE2 tyrosine kinase inhibition.Regorafenib demonstrated to increase the overall survival of patients with metastatic colorectal cancer and has been approved by the CFDA in 2017.

Apatinib, a small molecule receptor tyrosine kinase (RTK) inhibitor, targets the intracellular domain of the VEGFR-2 ATP binding site, and is the first anti-angiogenic therapy approved by the China Food and Drug Administration in December 2014 for the treatment of metastatic gastric cancer in third-line or later treatment. It is an orally bioavailable, small molecule agent which is thought to inhibit angiogenesis in cancer cells; specifically apatinib inhibits VEGF-mediated endothelial cell migration and proliferation thus blocking new blood vessel formation in tumor tissue. It is an investigational cancer drug currently undergoing clinical trials as a potential targeted treatment for metastatic gastric carcinoma, metastatic breast cancer ,advanced hepatocellular carcinoma and advanced colorectal cancer.

Apatinib are often used in advanced colorectal cancer for uses that are not within its approved indication for use.However, the knowledge gained from all uses of apatinib in this medical practice is often not realized because the data collected are not systematically characterized, aggregated, and analyzed in a way that can be relied upon to inform its further usage.

In some cases, a "traditional" clinical trial may be impractical or excessively challenging to conduct. Ethical issues regarding treatment assignment, and other similar challenges, may present themsevels when developing and attempting to execute a high quality clinical trial. Analyses of real-world data(RWD), using appropriate methods, may in some cases provide similar information with comparable or even superior characteristics to information collected and analyzed through a traditional clinical trial. For example, RWD collected using a randomized exposure assignment within a registry can provide a sufficient number of patients for powered subgroup analyses.

the investigators will evaluate the efficacy and safety for Apatinib combine with other chemotherapy regimens as the neoadjuvant therapy in advanced colorectal cancer in a real world study setting. This study leveraging RWD can potentially provide information on a wider patient population, thus providing information that cannot be obtained through a traditional clinical trial alone.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age of 18 years or older.
• Histological or cytological confirmation of adenocarcinoma of the colon or/and rectum;
• Stage TxNxM1 (truly metastatic disease) with liver metastases only.
• Patients should be voluntary to the trial and provide with signed informed consent.
• The researchers believe patients can benefit from the study.

Exclusion Criteria:

• Patients with a known history of allergic reactions and/or hypersensitivity attributed to apatinib or its accessories.
• Pregnant or lactating women
• Patients with Apatinib contraindications
• Patients of doctors considered unsuitable for the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: FOLFOX regimen; FOLFOX regime alone.	Drug: FOLFOX regimen; FOLFOX(Oxaliplatin 85 mg/m² IV infusion and leucovorin 200 mg/m² IV infusion， followed by Fluorouracil 400 mg/m² IV bolus , followed by Fluorouracil 600 mg/m²/h IV infusionas a 22-hour continuous infusion). Repeat cycle every 2 weeks for a total of 6 cycl
Experimental: Apatinib and FOLFOX regimen; Apatinib combine with FOLFOX regimen.	Drug: apatinib and FOLFOX regimen; Apatinib, 500mg p.o. qd, Repeat cycle every 2 weeks for a total of 6 cycles. FOLFOX regime, Repeat cycle every 2 weeks for a total of 6 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Progression-free survival is defined as the time from randomization to progression (RECIST v1.1 criteria) or death. Patients alive without progression will be censored at the last follow-up.	8 months
R0 ,R1 or R2 resection	Number of patients (%) with hepatic metastases R0 ,R1 or R2 resection.	at least 4-6 weeks after the end of chemotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Overall survival is defined as the time from randomization to death any cause or last follow-up news for patients alive (censored data).	14 months
ORR(objective response rate)	The objective response rate (CR and PR) will be evaluated by the investigator with RECIST v1.1 criteria after 4 cycles.	after 8 weeks

Collaborators and Investigators

• Sponsor: Sichuan Provincial People's Hospital
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Study Chair: Gaoping Gaoping, doctor, Sichuan Province Hospital

Publications and helpful links

General Publications

• Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, Wang Z, Wang Q, Ouyang X, Yang Y, Ba Y, Liang J, Lin X, Luo D, Zheng R, Wang X, Sun G, Wang L, Zheng L, Guo H, Wu J, Xu N, Yang J, Zhang H, Cheng Y, Wang N, Chen L, Fan Z, Sun P, Yu H. Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. J Clin Oncol. 2016 May 1;34(13):1448-54. doi: 10.1200/JCO.2015.63.5995. Epub 2016 Feb 16.

Helpful Links

• descriptions about real world study issued by the FDA

Study record dates

Study Major Dates

• Study Start (Anticipated): January 31, 2018
• Primary Completion (Anticipated): August 1, 2020
• Study Completion (Anticipated): September 1, 2020

Study Registration Dates

• First Submitted: December 8, 2017
• First Submitted That Met QC Criteria: December 14, 2017
• First Posted (Actual): December 19, 2017

Study Record Updates

• Last Update Posted (Actual): December 19, 2017
• Last Update Submitted That Met QC Criteria: December 14, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: apatinib
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Protein Kinase Inhibitors; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Apatinib
• Other Study ID Numbers: APTN-CRC-201712

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No