The Efficacy and Drug Resistance Molecular Biology of Apatinib Combined With EGFR-TK1 Treated for Advanced Slow-progressed Non-Small Cell Lung Cancer (NSCLC)

Patients with advanced non-small cell lung cancer (NSCLC) who progress slowly after Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors（EGFR-TKI）resistance. The purpose of this study is to investigate the efficacy and drug resistance mechanism of Apatinib combine with EGFR-TK1 treated for advanced slow progressed non-small cell lung cancer and provide new treatment options.

Study Overview

• Status: Unknown
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Apatinib（250mg/d） combined with EGFR-TKI

Detailed Description

Epidermal growth factor receptor Tyrosine kinase inhibitor (EGFR TKI) have been approved to treat NSCLC harboring EGFR mutation as first-line therapy. However, a large proportion of patients would become acquired resistant of EGFR-TKI after about one year although initially sensitivity. Previous studies demonstrated that the anti-angiogenesis combined with EGFR-TKI in slow-progressed EGFR mutation-positive non-small cell lung cancer achieved good efficacy and disease control rates, prolonged the progression free survival. The present study is aim to expand the number of samples to monitor resistance-related genes and tumor cells. Furthermore, to investigate the mechanism of anti-angiogenesis combine with EGFR-TKI and provide the theory for the use and promotion of clinically protocols. In this study, the primary objective is the objective response rates and the secondary goal are disease control rates, overall survival, progression free survival and drug safety.

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

Contacts and Locations

• Study Contact: Name: Liyan Xu, MD; Phone Number: 86-89509157; Email: xuliyan2009@yahoo.cn
• Study Contact Backup: Name: Jing Liu; Phone Number: 86-89509157

Study Locations

• China
  • Beijing, China
    • Recruiting
    • The Beijing Chest Hospital
    • Contact: Liyan Xu, MD; Email: xuliyan2009@yahoo.cn
    • Principal Investigator: Liyan Xu, MD

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. Informed consent should be obtained before treatment. Patients with good compliance.
2. Histologically or cytologically confirmed IIIB/IV NSCLC.
3. Progress in the treatment of EGFR TKI.
4. Aged from 18 to 75 years (18 and 75 years are included); Gender Not Required.
5. ECOG PS 0-1.
6. Life expectancy ≥ 3 months.
7. At least one measurable lesion (meet the requirements of the standard Response Evaluation Criteria In Solid Tumors (RESCIST) version 1.1). If the lesions that have received local treatment (radiation, radiofrequency, intervention, etc.) are the only lesions, it is required to have clear imaging progress.

Exclusion Criteria:

1. Uncontrolled hypertension (systolic ≥140mmHg and/or diastolic ≥90mmHg after medication treatment); Poor control of blood sugar.
2. Acute phase of cerebral infarction, or recovery period <2 months.
3. A variety of factors that affect the absorption of oral medications (such as inability to swallow, nausea and vomiting, chronic diarrhea, intestinal obstruction, etc.)
4. Patients with a risk of gastrointestinal bleeding may not be enrolled, including the following: (1) active digestive ulcer lesions, and fecal occult blood (++); (2) a history of melena and hematemesis within 2 months. Simple fecal occult blood (+) is not an exclusion criterion.
5. Coagulation abnormality (INR>1.5×ULN, APTT>1.5×ULN), with bleeding tendency.
6. Urine protein ≥ ++ or confirmed 24-hour urine protein quantitation > 1.0 g.
7. Pregnant or lactating women.
8. Severe liver and kidney dysfunction (grade 4) .
9. Allergic to any ingredient of apatinib mesylate.
10. A history of abuse of psychotropic substances and are unable to quit smoking or mental disorders.
11. According to the investigator's judgment, people with concomitant diseases that seriously endanger the safety of the patient or affect the patient's completion of the study.
12. Surgery, major trauma or fracture, within 4 weeks before the treatment or unhealed wound before treatment.
13. Severe heart disease, such as grade III or above (NYHA standard) congestive heart failure, grade III or above (CCS standard) angina, a history of myocardial infarction within 6 months before the treatment, or medication treated arrhythmia.
14. Brain metastasis and meningeal metastasis.

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 combined with EGFR-TKI; Apatinib 250 millgram（mg/day（d））combined with EGFR-TKI	Drug: Apatinib（250mg/d） combined with EGFR-TKI; Patients with advanced non-small cell lung cancer (NSCLC) who had treated with EGFR-TKI and progressed slowly because of resistance are underwent with apatinib mesylate and continuous EGFR-TKI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rates (ORR)	Objective response rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response according to Response Evaluation Criteria in Solid Tumors 1.1（RECIST1.1）	two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	Disease Control Rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response + Stable Disease according to radiological assessments.	two years
Overall survival (OS)	Time from randomization to death for any cause.	two years
Progression free survival (PFS)	PFS defined as date of randomization until the date of objectively determined progression defined by Response Evaluation Criteria in Solid Tumors criteria or death from any cause, whichever is first.	two years
Drug safety: Number of participants with treatment-related adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	two years

Collaborators and Investigators

• Sponsor: Beijing Chest Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: January 14, 2019
• First Submitted That Met QC Criteria: January 18, 2019
• First Posted (Actual): January 22, 2019

Study Record Updates

• Last Update Posted (Actual): January 22, 2019
• Last Update Submitted That Met QC Criteria: January 18, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Non Small Cell Lung Cancer; Apatinib; EGFR TKI; slowly progress
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: BeijingCH002

Drug and device information, study documents

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