mFOLFOX6 Chemotherapy With Apatinib as Postoperative Treatment in Stage IIIB or IIIC Colorectal Cancer

Exploratory Study on the Efficacy and the Safety of mFOLFOX6 Chemotherapy With Apatinib as Postoperative Treatment in Stage IIIB or IIIC Colorectal Cancer

This study will focus on postoperative patients of stage IIIB or stage IIIC colorectal cancer. These patients will start to accept chemotherapy in 3-4 weeks after operation, these patients were randomly divided into two groups, one group will accept adjuvant chemotherapy of mFOLFOX6; another group will use mFOLFOX6 combined with apatinib. The efficacy and safety of adjuvant chemotherapy will be compared between the two groups. Disease-free survival, overall survival, incidence of adverse reaction of chemotherapy and postoperative quality of life will be recorded.

Study Overview

• Status: Completed
• Conditions: Apatinib
• Intervention / Treatment: Drug: Apatinib; Drug: Oxaliplatin; Drug: 5-fluorouracil

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200040
    • Huashan Hospital Affiliated to Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. signed informed consent form;
2. confirmed as colorectal cancer by pathology, and the stage is IIIB /IIIC according to the NCCN guidelines;
3. patients with primary colorectal cancer;
4. radical resection of colon cancer (CME) or radical resection of rectal cancer (TME) has done;
5. 3~4 weeks after radical resection ;
6. patients did not receive any radiotherapy and chemotherapy before operation

Exclusion Criteria:

1. emergency operation for colorectal cancer patients;
2. the situation after operation can not tolerance for systemic adjuvant chemotherapy (hemoglobin <95g/L, white blood cell <3 * 109/L, granulocyte <1.5 * 109/L and platelet <75 * 109/L, bilirubin>2.5N, alanine aminotransferase >2.5N, alkaline phosphatase >2.5N, urea nitrogen >2.5N, creatinine >2.5N, proteinuria, hematuria, temperature of >38 degree);
3. serious diseases such as cardiac insufficiency, respiratory insufficiency, liver and kidney dysfunction, serious blood diseases;
4. patients participated in other clinical trials at the same time;
5. pregnant or perinatal women;
6. combined with other malignant tumors;
7. a history of neuropsychiatric disorders;
8. patients have used anti angiogenesis targeted drugs (such as bevacizumab, cetuximab);
9. patients had a history of severe trauma within 4 weeks before admission;
10. allergic to chemotherapy drugs or apatinib;
11. active bleeding, ulcers, intestinal perforation, intestinal obstruction, hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: mFOLFOX6 & apatinib; oxaliplatin 85mg/m2 intravenous infusion for 2 hours, intravenous infusion of leucovorin 400mg/m2 for 2 hours, intravenous infusion of 5- fluorouracil 400mg/m2, first days; 5- fluorouracil 2400mg/m2 continuous intravenous infusion for 46-48 hours, repeated 1 time every two weeks, a total of 12 cycles, 24 weeks. Patients also take apatinib, 1 time daily, 500mg each time, lasting 1 year, from the first chemotherapy of mFOLFOX6.	Drug: Apatinib; Apatinib tablet; Other Names: YN968D1; Drug: Oxaliplatin; Oxaliplatin Intravenous; Other Names: Eloxatin; Drug: 5-fluorouracil; 5-fluorouracil Intravenous; Other Names: Adrucil, Carac, Efudex, Efudix
ACTIVE_COMPARATOR: mFOLFOX6; oxaliplatin 85mg/m2 intravenous infusion for 2 hours, intravenous infusion of leucovorin 400mg/m2 for 2 hours, intravenous infusion of 5- fluorouracil 400mg/m2, first days; 5- fluorouracil 2400mg/m2 continuous intravenous infusion for 46-48 hours, repeated 1 time every two weeks, a total of 12 cycles, 24 weeks.	Drug: Oxaliplatin; Oxaliplatin Intravenous; Other Names: Eloxatin; Drug: 5-fluorouracil; 5-fluorouracil Intravenous; Other Names: Adrucil, Carac, Efudex, Efudix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease-free survival	observe the recurrence of colorectal cancer after operation	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	observe the postoperative survival rate in patients with stage IIIB and IIIC colorectal cancer	5 years
incidence of adverse reactions after chemotherapy	observe the adverse reaction of apatinib or combined chemotherapy using apatinib	one year

Collaborators and Investigators

• Sponsor: Huashan Hospital

Publications and helpful links

General Publications

• Scott AJ, Messersmith WA, Jimeno A. Apatinib: a promising oral antiangiogenic agent in the treatment of multiple solid tumors. Drugs Today (Barc). 2015 Apr;51(4):223-9. doi: 10.1358/dot.2015.51.4.2320599.
• Mi YJ, Liang YJ, Huang HB, Zhao HY, Wu CP, Wang F, Tao LY, Zhang CZ, Dai CL, Tiwari AK, Ma XX, To KK, Ambudkar SV, Chen ZS, Fu LW. Apatinib (YN968D1) reverses multidrug resistance by inhibiting the efflux function of multiple ATP-binding cassette transporters. Cancer Res. 2010 Oct 15;70(20):7981-91. doi: 10.1158/0008-5472.CAN-10-0111. Epub 2010 Sep 28.
• Tong XZ, Wang F, Liang S, Zhang X, He JH, Chen XG, Liang YJ, Mi YJ, To KK, Fu LW. Apatinib (YN968D1) enhances the efficacy of conventional chemotherapeutical drugs in side population cells and ABCB1-overexpressing leukemia cells. Biochem Pharmacol. 2012 Mar 1;83(5):586-97. doi: 10.1016/j.bcp.2011.12.007. Epub 2011 Dec 16.
• Tian S, Quan H, Xie C, Guo H, Lu F, Xu Y, Li J, Lou L. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci. 2011 Jul;102(7):1374-80. doi: 10.1111/j.1349-7006.2011.01939.x. Epub 2011 May 9.
• Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, Tong RT, Chung DC, Sahani DV, Kalva SP, Kozin SV, Mino M, Cohen KS, Scadden DT, Hartford AC, Fischman AJ, Clark JW, Ryan DP, Zhu AX, Blaszkowsky LS, Chen HX, Shellito PC, Lauwers GY, Jain RK. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med. 2004 Feb;10(2):145-7. doi: 10.1038/nm988. Epub 2004 Jan 25. Erratum In: Nat Med. 2004 Jun;10(6):649.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 12, 2018
• Primary Completion (ACTUAL): December 22, 2022
• Study Completion (ACTUAL): December 31, 2022

Study Registration Dates

• First Submitted: November 23, 2017
• First Submitted That Met QC Criteria: December 3, 2017
• First Posted (ACTUAL): December 7, 2017

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2023
• Last Update Submitted That Met QC Criteria: February 12, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• 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; Protein Kinase Inhibitors; Fluorouracil; Oxaliplatin; Apatinib
• Other Study ID Numbers: KY2017-299

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: our study protocol,statistical analysis plan,informed consent form and clinical study report are Chinese.

Drug and device information, study documents

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