Apatinib Combined With Paclitaxol as Second Line Therapy for Advanced Gastric Cancer.

A Phase II Multicenter, Randomized, Double-blind Study of Apatinib Combined With Paclitaxol Versus Placebo With Paclitaxol as Second Line Therapy for Advanced Gastric / Esophagogastric Junction Adenocarcinoma With Peritoneal Metastasis.

This multicenter, randomized, double-blind study will evaluate the efficacy and safety of apatinib combined with paclitaxol versus placebo combined with paclitaxol in advanced gastric cancer or gastroesophageal junction carcinoma patients with peritoneal metastasis.

Patients will be randomized to one treatment arm: Arm A: apatinib 500mg qd, Paclitaxol 80mg/m2, d1, d8, d15,every 4 weeks ; Arm B: placebo 500mg qd, Paclitaxol 80mg/m2, d1, d8, d15,every 4 weeks ; Tumor assessment will be done every 8 weeks according to RECIST 1.1. The primary endpoint is progression free survival (PFS).

Study Overview

• Status: Unknown
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: Apatinib; Drug: Placebos

Detailed Description

Gastric cancer is the second most common cause of cancer-related deaths worldwide, and most patients are diagnozed at advanced stage in China. Peritoneal metastasis is the most common metastatic site. For gastric cancer patients with peritoneal metastasis, chemotherapy can bring survival benefit versus best sportive care. Paclitaxol is the standard second line chemotherapy for advanced gastric cancer patients.

Apatinib mesylate is a small-molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor (TKI). It has been approved as third-line treatment for patients with advanced gastric adenocarcinoma in China.

This multicenter, randomized, double-blind study will evaluate the efficacy and safety of apatinib combined with paclitaxol versus placebo combined with paclitaxol in advanced gastric cancer or gastroesophageal junction carcinoma patients with peritoneal metastasis.

• Study Type: Interventional
• Enrollment (Anticipated): 110
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Foshan, Guangdong, China
      • Recruiting
      • Foshan people's Hospital
      • Contact: Wei Wang; Phone Number: 075783161035; Email: m18038863618@163.com
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Cancer center of Sun Yat-sen University
      • Contact: Miao-Zhen Qiu, MD, PhD; Phone Number: 86-020-87342490; Email: qiumzh@sysucc.org.cn
      • Contact: Fenghua Wang, MD, PhD; Phone Number: 86-020-87342490; Email: wangfh@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult patients, aged between 18 and 75 years old;
2. Histologically confirmed advanced or metastatic adenocarcinoma of gastric cancer(AGC) , including adenocarcinoma of the gastroesophageal junction ;
3. At least one measurable and evaluable disease based on response evaluation criteria in solid tumors (RECIST v1.1); and confirmed as peritoneal metastasis by CT scan or laparoscope
4. Patients must have received one prior chemotherapy regimen for AGC;First-line therapy must have included a combination of at least a platinum-based treatment given concurrently, and must have experienced disease progression during or after first-line therapy for their disease;
5. Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1;
6. Life expectancy of more than 3 months;
7. Duration from the last therapy is more than 6 weeks for nitroso or mitomycin, More than 4 weeks for other cytotoxic agents, operation or radiotherapy;
8. Adequate hepatic, renal, heart, and hematologic functions ( hemoglobin≥ 90g/L, platelets ≥ 80 × 10*9/L, neutrophil ≥1.5 × 10*9/L, serum creatinine≤ 1.5mg/dl, total bilirubin ≤1.5 ×ULN, and serum transaminase≤2.5×ULN)

Exclusion Criteria:

1. Pregnant or lactating women;
2. History of other malignancies except cured basal cell carcinoma of skin and carcinoma insitu of uterine cervix;
3. Prior chemotherapy regimen have included taxane (docetaxel or paclitaxel); 4. Uncontrolled hypertension;

5. Intercurrence with one of the following: coronary artery disease, arrhythmia and heart failure; 6. Urine protein>grade 1; 7. Any factors that influence the usage of oral administration; 8. Patients with a clear tendency of gastrointestinal bleeding; 9. Abnormal coagulation function(INR≥1.5, APTT≥1.5 ULN); 10. Abuse of alcohol or drugs; 11. Less than 4 weeks from the last clinical trial; 12. Prior treatment with antivascular endothelial growth factor or the other anti angiogenesis therapy; 13. Evidence of central nervous system(CNS) metastasis; 14. Disability of serious uncontrolled intercurrence infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Apatinib: 500mg, po, qd, every 4 weeks Paclitaxol: 80mg/m2, d1, d8, d15, every 4 weeks	Drug: Apatinib; Apatinib 500mg, po, qd, every 4 weeks Paclitaxol: 80mg/m2, d1, d8, d15, every 4 weeks; Other Names: Paclitaxol
Placebo Comparator: Placebo group; Placebo: 500mg, po, qd, every 4 weeks Paclitaxol: 80mg/m2, d1, d8, d15, every 4 weeks	Drug: Placebos; Placebo: 500mg, po, qd, every 4 weeks Paclitaxol: 80mg/m2, d1, d8, d15, every 4 weeks; Other Names: Paclitaxol

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	Approximately 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	The time from randomize to death	Approximately 3 years
Objective response rate (ORR)	The rate of complete response and partial response according to RECIST guidelines	Approximately 1 year
Disease control rate(DCR)	The rate of complete response , partial response and stable disease according to RECIST guidelines	Approximately 1 year
Safety (incidence of adverse events) [	Incidence of adverse events	Approximately 1 year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2017
• Primary Completion (Anticipated): January 31, 2020
• Study Completion (Anticipated): January 31, 2020

Study Registration Dates

• First Submitted: May 5, 2017
• First Submitted That Met QC Criteria: May 5, 2017
• First Posted (Actual): May 9, 2017

Study Record Updates

• Last Update Posted (Actual): May 9, 2017
• Last Update Submitted That Met QC Criteria: May 5, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Gastric cancer; Apatinib; Peritoneal metastasis; Second-line chemotherapy; Paclitaxol
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: Apatinib_GC

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