Clinical Study of Apatinib and XELOX Combination Regimen to Treat Colorectal Cancer Patients

Colorectal Neoplasms Clinical Trial

Official title:

A Phase II Clinical Trial Study on Apatinib and XELOX Combination Regimen in the First-line Treatment of End-stage Colorectal Cancer Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02829385
• Other study ID #: LZU-123
• Status: Recruiting
• Phase: Phase 2
• First received: July 8, 2016
• Last updated: July 11, 2016
• Start date: June 2016
• Est. completion date: September 2018

Study information

• Verified date: July 2016
• Source: LanZhou University
• Contact: Shoucheng Ma, Master
• Phone: (86)13893453504
• Email: mashoucheng[@]medmail.com.cn
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study makes an observation over the objective response rate of Apatinib and XELOX combination regimen in the first-line treatment of metastatic colorectal cancer. All the participants will receive the treatment of Apatinib and XELOX combination regimen.

Description:

XELOX chemotherapy is an effective therapy for metastatic colorectal cancer as first-line treatment.

Apatinib is a small-molecule tyrosine kinase inhibitor (TKI) that highly selectively binds to and strongly inhibits vascular endothelial growth factor receptor 2 (VEGFR-2), with a decrease in VEGF-mediated endothelial cell migration, proliferation, and tumor microvascular density. A phase II trail of Apatinib has been demonstrated that Apatinib is safe to treat the metastatic colorectal cancer and the disease control rate can reach 50%.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 53
• Est. completion date: September 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Unresectable colorectal cancer confirmed by histological means with measurable indication(a minimum size of 10mm by spiral CT scan,which meets the criteria of RECIST 1.1).

• Time interval traced back to the latest administration of xelox and folfox combination must be no less than 1 year.

• age range: =18 and =75.

• ECOG PS scale 0 or 1;expected survival time =12 weeks.

• Sufficient blood function:absolute neutrophil count (ANC) =1.5×109/L, platelet count =80×109/L and hemoglobin=9g/dL.

• Sufficient hepatic function:total bilirubin =1.5 times upper normal limit(ULN), AST =2.5 times ULN, ALT =2.5 times ULN and AKP =5 times ULN.

*AST,ALT relevant criteria alters into AST =5 times ULN and ALT =5 times ULN if with hepatic metastasis.

• sufficient renal function: serum creatinin =ULN, creatinine clearance rate =60 mL/min

• Female patients under age 50 with complete uterus must be tested negative for pregnancy within 28 days before enrollment (except for those who suffered amenorrhea for more than 24 months). If the pregnancy test was carried out more than 7 days before the first administration, then the urine pregnancy test is required for validation. (within the 7-day interval before administration)

• Informed consent subscription. (The consent should be approved by independent Ethics Committee, and signed by patients before any substantial trial is initiated.)

Exclusion Criteria:

• Have got other malignant tumors within last 5 years, excluding basal cell skin cancer and cervical carcinoma in situ that has already been cured.

• With evidence of CNS metastasis, even if the treatment had been carried out before, patients with doubts of CNS metastasis should be conducted MRI or enhanced CT scan on within 28 days before enrollment for ruling out.

• AST =2.5 times ULN and/or ALT =2.5 times ULN

• Had been treated with chemotherapy for last 12 months

• Had been treated with radiotherapy (except for palliative radiotherapy with evaluable focus outside radiotherapy field on purpose of alleviating pains)

• With any uncontrolled systemic disease, including active infection, hypertension without treatment, diabetes mellitus, angina pectoris, congestive heart failure, myocardial infarction, severe arrhythmia requires treatment and hepatic/renal/metabolic diseases

• Taking experimental treatment from another clinical trial study.

• Being allergic to any relevant chemotherapy drug.

• With evidence-proved other diseases, neural or metabolic disorders, physical or lab examination abnormalities, which might be contraindication of study drugs or leading to treating-related lethal complications.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms

Intervention

Drug:
• Apatinib and XELOX combined treatment group
Apatinib Mesylate Tablets 500 mg P.O.d1-21 and XELOX (oxaliplatin 130mg/? i.v. d1, capecitabine 1000mg P.O. d1-d14) Every 3-week time is a cycle until PD or intolerance of drug toxicity occurs.

Locations

Country	Name	City	State
China	Cancer Cnter,The First Hospital of Lanzhou University	Lanzhou	Gansu

Sponsors (1)

Lead Sponsor	Collaborator
Shoucheng Ma

Country where clinical trial is conducted

China, 

References & Publications (12)

Bruera G, Cannita K, Giordano AV, Vicentini R, Ficorella C, Ricevuto E. Effectiveness and safety of intensive triplet chemotherapy plus bevacizumab, FIr-B/FOx, in young-elderly metastatic colorectal cancer patients. Biomed Res Int. 2013;2013:143273. doi: — View Citation

Custodio A, Barriuso J, de Castro J, Martínez-Marín V, Moreno V, Rodríguez-Salas N, Feliu J. Molecular markers to predict outcome to antiangiogenic therapies in colorectal cancer: current evidence and future perspectives. Cancer Treat Rev. 2013 Dec;39(8): — View Citation

Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Blasinska-Morawiec M, Šmakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD. Panit — View Citation

Kara O, Duman BB, Kara B, Erdogan S, Parsak CK, Sakman G. Analysis of PTEN, VEGF, HER2 and P53 status in determining colorectal cancer benefit from bevacizumab therapy. Asian Pac J Cancer Prev. 2012;13(12):6397-401. — View Citation

Kishiki T, Ohnishi H, Masaki T, Ohtsuka K, Ohkura Y, Furuse J, Watanabe T, Sugiyama M. Overexpression of MET is a new predictive marker for anti-EGFR therapy in metastatic colorectal cancer with wild-type KRAS. Cancer Chemother Pharmacol. 2014 Apr;73(4):7 — View Citation

Kiss I, Bortlicek Z, Melichar B, Poprach A, Halamkova J, Vyzula R, Dusek L, Buchler T. Efficacy and toxicity of bevacizumab on combination with chemotherapy in different lines of treatment for metastatic colorectal carcinoma. Anticancer Res. 2014 Feb;34(2 — View 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. R — View Citation

Naeim A, Ward PR, Wang HJ, Dichmann R, Liem AK, Chan D, Patel R, Hu EH, Tchekmedyian NS, Wainberg ZA, Hecht JR. A phase II trial of frontline capecitabine and bevacizumab in poor performance status and/or elderly patients with metastatic colorectal cancer — View Citation

Peeters M, Oliner KS, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, He P, Yu H, Koukakis R, Terwey JH, Jung AS, Sidhu R, Patterson SD. Analysis of K — View Citation

Sclafani F, Cunningham D. Bevacizumab in elderly patients with metastatic colorectal cancer. J Geriatr Oncol. 2014 Jan;5(1):78-88. doi: 10.1016/j.jgo.2013.08.006. Epub 2013 Sep 20. Review. — View Citation

Simkens LH, van Tinteren H, May A, ten Tije AJ, Creemers GJ, Loosveld OJ, de Jongh FE, Erdkamp FL, Erjavec Z, van der Torren AM, Tol J, Braun HJ, Nieboer P, van der Hoeven JJ, Haasjes JG, Jansen RL, Wals J, Cats A, Derleyn VA, Honkoop AH, Mol L, Punt CJ, — View Citation

Tabernero J, Van Cutsem E, Lakomý R, Prausová J, Ruff P, van Hazel GA, Moiseyenko VM, Ferry DR, McKendrick JJ, Soussan-Lazard K, Chevalier S, Allegra CJ. Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatme — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	ORR=complete response (CR) + partial response (PR) .And expected ORR is 0.55.	up to 9 months	No
Secondary	Progression-free Survival (PFS)	time from randomization to documented progressive disease or death due to any cause, whichever occurs first	up to 2 years	No
Secondary	Overall Survival (OS)		up to 2 years	No