APatinib Plus Chemotherapy vErsus Chemotherapy As First-line Treatment for Advanced NSCLC (APPEAL)

A Multicenter Phase II Trial of Pemetrexed Plus Carboplatin With or Without Apatinib in Patients With Advanced Non-small Cell Lung Cancer Without EGFR Mutation, ALK Gene Rearrangement, and ROS1 Gene Rearrangement

The purpose of this study is to studying the addition of apatinib with chemotherapy to investigate the efficacy and safety of apatinib in combination with chemotherapy in patients with advanced NSCLC.

Study Overview

• Status: Withdrawn
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: Apatinib; Drug: Pemetrexed; Drug: Carboplatin

Detailed Description

Platinum-based chemotherapy is the recommended therapeutic approach for patients with advanced non-small cell lung cancer (NSCLC) without EGFR mutation, ALK gene rearrangement, and ROS1 gene rearrangement. However, the prognosis of advanced NSCLC remains poor. Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2. Apatinib has been proved to be effective and safe in heavily pretreated patients with gastric cancer. This study is to studying the addition of apatinib with chemotherapy to investigate the efficacy and safety of apatinib in combination with chemotherapy in patients with advanced NSCLC.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Target population is advanced NSCLC (IIIB-IV) without EGFR mutation, ALK gene rearrangement, and ROS1 gene rearrangement.
• Written informed consent provided.
• Male and female patients aged ≥18 years, < 75 years.
• Able to comply with the required protocol and follow-up procedures, and able to receive oral medications.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Life expectancy ≥12 weeks.
• Adequate hematological function: Absolute neutrophil count (ANC) ≥2.0 x 109/L, and Platelet count ≥100 x 109/L, and Hemoglobin ≥9 g/dL (may be transfused to maintain or exceed this level).
• Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN in subjects without liver metastases; ≤ 5 x ULN in subjects with liver metastases.
• Adequate renal function: Serum creatinine ≤ 1.25 x ULN, or ≥ 60 ml/min.
• Female subjects should not be pregnant or breast-feeding.

Exclusion Criteria:

• Known severe hypersensitivity to apatinib or any of the excipients of this product.
• Inability to comply with protocol or study procedures.
• A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study.
• A serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease.
• Patients with prior chemotherapy or therapy with systemic anti-tumour therapy (e.g. monoclonal antibody therapy).
• Patients with prior radiotherapy
• History of another malignancy in the last 5 years with the exception of the following: other malignancies cured by surgery alone and having a continuous disease-free interval of 5 years are permitted. Cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix are permitted.
• Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).
• Eye inflammation or eye infection not fully treated or conditions predisposing the subject to this.
• Evidence of any other disease, neurological or metabolic dysfunction, physical examination or laboratory finding giving reasonable suspicion of a disease or condition that contraindicated the use of an investigational drug or puts the subject at high risk for treatment-related complications.
• Patient who has active serious infection (e.g. pyrexia of or 38.0℃ over)

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; Patients were given pemetrexed (500 mg/m2) plus carboplatin (AUC =5) plus apatinib. Apatinib was given 850 mg per day orally at day one of chemotherapy.	Drug: Apatinib; Apatinib was given 850 mg per day orally.; Drug: Pemetrexed; pemetrexed (500 mg/m2); Drug: Carboplatin; carboplatin (AUC =5)
Active Comparator: Control; Patients were given pemetrexed (500 mg/m2) plus carboplatin (AUC =5).	Drug: Pemetrexed; pemetrexed (500 mg/m2); Drug: Carboplatin; carboplatin (AUC =5)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival was assessed from randomization to death as a result of any cause.	1 year after the last patient is randomized

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	Disease-free survival was assessed from randomization to disease recurrence or death as a result of any cause.	1 year after the last patient is randomized
Number of Participants with Adverse Events	To assess if the addition of apatinib to chemotherapy is safe.	1 year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2017
• Primary Completion (Estimated): May 20, 2025
• Study Completion (Estimated): May 20, 2027

Study Registration Dates

• First Submitted: May 22, 2017
• First Submitted That Met QC Criteria: May 22, 2017
• First Posted (Actual): May 24, 2017

Study Record Updates

• Last Update Posted (Actual): December 10, 2024
• Last Update Submitted That Met QC Criteria: December 5, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Protein Kinase Inhibitors; Pemetrexed; Carboplatin; Apatinib
• Other Study ID Numbers: GASTO1006

Drug and device information, study documents

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