Phase III Study of Apatinib Tablets in the Treatment of Advanced or Metastatic Gastric Cancer

A Randomized, Double Blinded, Placebo Controlled Multicenter Phase III Study of Apatinib Mesylate Tablets in the Treatment of Advanced or Metastatic Gastric Cancer

Apatinib is a tyrosin-inhibitor agent targeting at vascular endothelial growth factor receptor (VEGFR), and it's anti-angiogenesis effect has been viewed in preclinical tests. The investigators' phase I study has shown that the drug's toxicity is manageable and the maximum tolerable daily dose is 850 mg. The purpose of this study is to determine whether apatinib can improve progression free survival or overall survival compared with placebo in patients with metastatic gastric carcinoma who failed two lines of chemotherapy.

Study Overview

• Status: Completed
• Conditions: Advanced or Metastatic Gastric Cancer
• Intervention / Treatment: Drug: apatinib; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 267
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • The 81 Hosiptal of PLA
  • Shanghai
    • Shanghai, Shanghai, China
      • Fudan University Cancer Hospital

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:

• ≥ 18 and ≤ 70 years of age
• Histological confirmed advanced or metastatic adenocarcinoma of the stomach
• Have failed for at least 2 lines of chemotherapy
• Life expectancy of at least 12 weeks.
• Eastern Cooperative Oncology Group Performance Status of 0 or 1 within 1 week before randomization.
• At least one measurable lesion beyond stomach (larger than 10 mm in diameter by spiral CT scan)
• Duration from the last therapy is more than 6 weeks for nitroso or mitomycin
• More than 4 weeks for operation or radiotherapy
• More than 4 weeks for cytotoxic agents or growth inhibitors
• Adequate hepatic, renal, heart, and hematologic functions (HB ≥ 90g/L,platelets > 80 ×10 E+9/L, neutrophil > 1.5 × 10 E+9/L, serum creatinine ≤ 1× upper limit of normal(ULN), bilirubin < 1.25× ULN, and serum transaminase ≤ 2.5× ULN).

Exclusion Criteria:

• Pregnant or lactating women
• History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg).
• Any factors that influence the usage of oral administration; Evidence of Central Nerves System(CNS) metastasis
• Intercurrence with one of the following: coronary artery disease, arrhythmia ,heart failure and proteinuria ≥ (+)
• International Normalize Ratio (INR) > 1.5 and activated partial thromboplastin time（APPT） > 1.5 × ULN
• Abuse of alcohol or drugs
• Certain possibility of gastric or intestine hemorrhage
• Less than 4 weeks from the last clinical trial
• Prior VEGFR inhibitor treatment
• Disability of serious uncontrolled intercurrence infection Objective evidence of previous or current pulmonary fibrosis history, interstitial pneumonia, Pneumoconiosis, radiation pneumonitis, drug-related pneumonia, Pulmonary function damaged seriously etc.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: placebo; placebo qd p.o. until disease progression or intolerable toxicity or patients withdrawal of consent
Experimental: apatinib	Drug: apatinib; apatinib 850 mg qd p.o. until disease progression or intolerable toxicity or patients withdrawal of consent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival(PFS)	Progression free survival of All the Evaluable Participants.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of diameters of target lesions, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	30 months
Overall Survival(OS)	Overall Survival of the Participants	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate(DCR)	Disease control is defined as the proportion of patients who had a best response rating of complete response, partial response, or stable disease, and lasted at least 4 weeks.	30 months
Objective Response Rate(ORR)	Objective Response Rate is defined as the proportion of patients with complete response(CR) or partial response(PR)	30 months
Percentage of Participants With Adverse Events		30 months

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Collaborators: Fudan University; The 81 Hospital of PLA
• Investigators: Principal Investigator: jin li, MD, PHD, Fudan University; Principal Investigator: Shukui Qin, MD, The 81 Hospital of PLA

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: January 13, 2012
• First Submitted That Met QC Criteria: January 15, 2012
• First Posted (Estimate): January 19, 2012

Study Record Updates

• Last Update Posted (Estimate): October 17, 2016
• Last Update Submitted That Met QC Criteria: August 30, 2016
• Last Verified: April 1, 2015

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; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: HENGRUI 20101208