Clinical Study of Apatinib Combined With Second - Line Chemotherapy for Metastatic Colorectal Cancer

A Randomized, Parallel-controlled, Exploratory Clinical Trial of Second-line Chemotherapy With Second-line Chemotherapy Versus Second-line Chemotherapy With Apatinib in the Treatment of Metastatic Colorectal Cancer

(1) Evaluate the efficacy of apatinib in combination with standard second-line chemotherapy for advanced colorectal cancer. Whether it can prolong Progression Free Survival (PFS), overall survival (OS) in patients with advanced colorectal cancer and reduce symptoms and improve quality of life compared with standard second-line chemotherapy; (2) Observe the safety of apatinib for the treatment of advanced colorectal cancer.

Study Overview

• Status: Unknown
• Conditions: Colorectal Neoplasms
• Intervention / Treatment: Drug: Apatinib; Drug: standard second-line chemotherapy

Detailed Description

Standard second line chemotherapy includes chemotherapy based on irinotecan or chemotherapy based on oxaliplatin.

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%.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liqiang Zhong; Phone Number: 15283572951; Email: zhongliqiang@163.com

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. Male or female aged 18 to 70 years old;
2. Histologically or cytologically proven patients with metastatic colorectal cancer have undergone a first-line standard regimen recommended by the NCCN guidelines for progression;
3. According to the RECIST 1.1 criteria, the patient has at least one target lesion that can measure the diameter;
4. ECOG PS ≤ 2;
5. Expected survival time of more than 12 weeks.

6. The level of organ function must meet the following requirements:

   Bone marrow: neutrophil count (ANC) ≥ 1.5 × 10^9/L, platelet ≥ 75 × 10^9/L, hemoglobin ≥ 90g/L.

   Liver: serum bilirubin ≤ 2 times the upper limit of normal, aminotransferase AST and ALT ≤ 2.5 times the normal upper limit.

   Kidney: Serum creatinine ≤1.5 times upper limit of normal.

7. Patient compliance is good;
8. Understand and voluntarily sign a written informed consent.

Exclusion Criteria:

1. Other previous or concurrent malignancy, except cured skin basal cell carcinoma and cervical carcinoma in situ;
2. Already known to be allergic to apatinib or any excipient;
3. Use unapproved drugs or other test medications within 4 weeks prior to enrollment;
4. There are many factors that affect oral medications (such as inability to swallow, chronic diarrhea and intestinal obstruction);
5. Patients with a history of CNS metastases or CNS metastases;
6. A history of bleeding, with any serious grading within 4 weeks prior to screening reaching a bleeding event of 3 degrees Celsius or greater in CTCAE4.0;
7. Serious infection;
8. Serious cardiovascular disease: uncontrolled hypertension, unstable angina, grade 3-4 heart failure (NYHA standard), congestive heart failure;
9. urinary routine urinary protein ≥ ++ and confirmed 24-hour urinary protein quantitation> 1.0 g;
10. Within 30 days after major surgery;
11. Thrombotic disease. Anemia or venous thrombosis occurred in the previous year, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, pulmonary embolism, etc.;
12. Those with history of psychotropic substance abuse who can not be abstinent or have mental disorders;
13. Have clinical symptoms, need clinical intervention pleural effusion or ascites;
14. At the investigator's discretion, there is a serious concomitant condition that compromises the patient's safety or affects the patient in completing the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apatinib group; Apatinib combined with second-line chemotherapy (5-Fu combined with irinotecan or oxaliplatin standard regimen ) Apatinib tablets: 500 mg po qd . Continuous medication, the cycle is consistent with the chemotherapy cycle. Oxaliplatin: Day 1, 130mg/m2, IV infusion. Capecitabine: Day 1-14, 1000mg/m2 Twice Daily, po. A total of 6 cycles, 3 weeks apart of chemotherapy.（Take CAPEOX for example）	Drug: Apatinib; Apatinib in combination with standard second-line chemotherapy for advanced colorectal cancer; Other Names: YN968D1; Drug: standard second-line chemotherapy; The second line standard chemotherapy regimen recommended by the NCCN; Other Names: FOLFOX、FOLFIRI、CapeOX
Placebo Comparator: Control group; Oxaliplatin: Day 1, 130mg/m2, IV infusion. Capecitabine: Day 1-14, 1000mg/m2 Twice Daily, po. A total of 6 cycles, 3 weeks apart of chemotherapy.（Take CAPEOX for example）	Drug: standard second-line chemotherapy; The second line standard chemotherapy regimen recommended by the NCCN; Other Names: FOLFOX、FOLFIRI、CapeOX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	the time from randomize to progression or death; RECIST guidelines were used to define all responses after patients had received every 4 weeks of therapy	Approximately 2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Defined as the time from randomize to death	Approximately 3 years
Objective Response Rate (ORR)	ORR=complete response (CR) + partial response (PR)	Approximately 2 years
Disease control rate(DCR)	Defined as the rate of complete response , partial response and stable disease according to RECIST guidelines	Approximately 2 years
Quality of life(QoL)	As measured by the European Organization for Research and Treatment of Cancer questionnaire (EORTC QLQ C30)	Approximately 2 year

Collaborators and Investigators

• Sponsor: Liqiang Zhong
• Investigators: Study Chair: Liqiang Zhong, Yibin Second People's Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): February 28, 2018
• Primary Completion (Anticipated): February 28, 2020
• Study Completion (Anticipated): February 28, 2021

Study Registration Dates

• First Submitted: January 22, 2018
• First Submitted That Met QC Criteria: January 22, 2018
• First Posted (Actual): January 29, 2018

Study Record Updates

• Last Update Posted (Actual): January 29, 2018
• Last Update Submitted That Met QC Criteria: January 22, 2018
• Last Verified: January 1, 2018

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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: ChiCTR1800014478

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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