Clinical trial NCT03377842: Apatinib Treatment as the Neoadjuvant Therapy in Advanced Colorectal Cancer
Official title: A Real World Study of Efficacy and Safety for Apatinib Treatment as the Neoadjuvant Therapy in Advanced Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Colorectal Cancer
Neoadjuvant Therapy
Keywords: apatinib
Lead sponsor: Sichuan Provincial People's Hospital
Sponsor class: OTHER
Collaborators: name: Jiangsu HengRui Medicine Co., Ltd.
First posted: 2017-12-19
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: R0 ,R1 or R2 resection
timeFrame: at least 4-6 weeks after the end of chemotherapy
measure: Progression-free survival (PFS)
timeFrame: 8 months
Secondary outcomes:
measure: ORR(objective response rate)
timeFrame: after 8 weeks
measure: Overall survival (OS)
timeFrame: 14 months
Other outcomes:
Locations:
Study officials:
affiliation: Sichuan province hospital
name: Gaoping Gaoping, doctor
role: STUDY_CHAIR
References:
citation: 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.