Apatinib Combined With POF for Second-line Treatment of Gastric Adenocarcinoma

Phase II Study on the Second-line Treatment of Gastric Adenocarcinoma With Apatinib Combined With POF(Paclitaxel Plus Oxaliplatin Plus 5-fluorouracil Plus Leucovorin)

In previous studies,the investigators found that POF (A combination of oxaliplatin, fluorouracil and Paclitaxel) regimen appears to be of good efficacy and is well tolerated in patients with advanced gastric cancer. Apatinib is an orally antiangiogenic agent. It was approved and launched in China in 2014 as a 3rd-line treatment for patients with advanced gastric cancer. Therefore, investigators conducted the dose escalation phase I study to explore the safety of combination of apatinib and POF as first-line treatment for advanced gastric cancer. Now the investigators are going to start a phase 2 trial with apatinib 500mg + POF as second-line therapy to investigate the efficacy and safety in the patients with advanced gastric cancer.

Study Overview

• Status: Unknown
• Conditions: Gastric Adenocarcinoma
• Intervention / Treatment: Drug: Apatinib; Drug: POF

• Study Type: Interventional
• Enrollment (Anticipated): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Fuzhou, China, 350014
    • Recruiting
    • Rongbo Lin
    • Contact: Rongbo Lin; Phone Number: 13705919382 13705919382; Email: rongbo_lin@163.com
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Recruiting
      • Rongbo Lin

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:

• Patients with advanced unresectable, histologically confirmed adenocarcinoma of the gastric or gastroesophageal junction.
• Previous first-treatment with chemotherapy or radiation therapy failed. Ability to take medications orally. With measurable lesions. Patients must have a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale.
• Without serious system dysfunction and could tolerate chemotherapy. With normal marrow, liver and renal function: a hemoglobin (HGB) of ≥100g/L (without blood transfusion during 14 days); a leucopenia count of ≥4.0×109/L; a platelet count of ≥100×109/L; a total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL); a creatinine (Cr) of ≤ 1.5 UNL; a creatinine clearance rate ≥ 50ml/min (Cockcroft-Gault); a alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤2.5 UNL or ≤5 UNL in case of liver metastasis.
• Life expectancy ≥3 months. With normal electrocardiogram results and no history of congestive heart failure.
• Without bleeding and thrombosis disease. With normal coagulation function: activated partial thromboplastin time (APTT), prothrombin time (PT) and INR, each ≤ 1.5 x ULN.
• Female subjects of child-bearing potential must agree to use contraceptive measures starting 1 week before the administration of the first dose of apatinib until 8 weeks after discontinuing study drug. Male subjects must agree to use contraceptive measures during the study and 8 weeks after last dose of study drug With written informed consent signed voluntarily by patients themselves or their supervisors witted by doctors.
• With good compliance and agree to accept follow-up of disease progression and adverse events.

Exclusion Criteria:

• Patients with a history of another neoplastic disease within the past three years, excluding basal cell carcinoma of the skin, cervical carcinoma in situ, or nonmetastatic prostate cancer.
• Patients with brain or central nervous system metastases, including leptomeningeal disease.
• Pregnant (positive pregnancy test) or breast feeding. Serious, non-healing wound, ulcer, or bone fracture. Significant cardiac disease as defined as: unstable angina, New York Heart Association (NYHA) grade II or greater, congestive heart failure, history of myocardial infarction within 6 months Evidence of bleeding diathesis or coagulopathy.
• History of a stroke or CVA within 6 months. Clinically significant peripheral vascular disease. Inability to comply with study and/or follow-up procedures. Patients with any other medical condition or reason, in that investigator's opinion, makes the patient unstable to participate in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Apatinib plus POF; Apatinib (500 mg qd p.o.) plus POF until disease progression or intolerable toxicity or refused by the patients.

Drug: Apatinib; Apatinib (500 mg qd p.o.) until disease progression or intolerable toxicity or refused by the patients.; Drug: POF; The POF regimen consisted of a 3-hour infusion of paclitaxel (135 mg/m2) followed by oxaliplatin (85 mg/m2) and Calcium Levofolinate (200 mg/m2).Subsequently, a 46-hour infusion of fluorouracil (2400 mg/m2) was administered using an ambulatory pump, repeating the cycle every 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	According to RECIST 1.1	From enrollment to 3 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	The length of time from enrollment until the time of progression of disease	From enrollment to progression of disease. Estimated about 12 months.
Overall survival	The length of time from enrollment until the time of death	From enrollment to death of patients. Estimated about 18 months
Toxicity According to NCI CTCAE 4.03 criteria	According to NCI CTCAE 4.03 criteria	From enrollment to 3 months after treatment

Collaborators and Investigators

• Sponsor: Fujian Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: December 23, 2018
• First Submitted That Met QC Criteria: December 25, 2018
• First Posted (Actual): December 27, 2018

Study Record Updates

• Last Update Posted (Actual): May 10, 2019
• Last Update Submitted That Met QC Criteria: May 8, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: FNF013

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