Gefitinib With Chemotherapy or Anti-angiogenesis in NSCLC Patients With Bim Deletion or Low EGFR Mutation Abundance

NCT03267654 | Unknown Phase 2

• 1 other identifier: SHENKANG
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, multicenter, randomized, phase II clinical trial, which aims to evaluate the effectiveness and safety of gefitinib versus combination of gefitinib and doublet chemotherapy or apatinib in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) activating mutation (exon 19 deletion or exon 21 L858R point mutation), accompanied with Bim deletion or low activating EGFR mutation abundance.

Conditions

Non-small-cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  From start of anti-cancer therapy until progression or death

  8 weeks

Secondary Outcomes (6)

• overall survival

  36 months

• objective response rate

  8 weeks

• disease control rate

  8 weeks

• duration of response

  8 weeks

• safety evaluation

  8 weeks

Study Arms (3)

gefitinib combined with chemotherapy

EXPERIMENTAL

gefitinib 250mg Qd combined with pemetrexed plus carboplatin: pemetrexed (500mg/m²day 1 intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days.

Drug: gefitinib combined with chemotherapy

gefitinib combined with apatinib

EXPERIMENTAL

gefitinib 250mg Qd combined with apatinib 250mg per 21 days

Drug: gefitinib combined with apatinib

gefitinib single agent

ACTIVE COMPARATOR

Advanced NSCLC patients with EGFR activating mutation (L858R, 19Del) received gefitinib 250mg Qd orally until progression, intolerable toxicity or death.

Drug: gefitinib single agent

Interventions

gefitinib combined with chemotherapy DRUG

Gefitinib 250mg, p.o., q.d., continuous regimens on an empty stomach or after meal for 2 hours until disease progression, intolerable toxicity or patient withdraw ICF. Pemetrexed (500mg/m²day 1 intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days. Every 3 weeks is a chemotherapy cycle, and 4 chemotherapy cycles is maximum limit.

Also known as: yiruike

gefitinib combined with chemotherapy

gefitinib combined with apatinib DRUG

gefitinib 250mg, p.o., q.d., continuous regimens on an empty stomach or after meal for 2 hours. Apatinib 250mg, p.o., q.d. per 21 days. until disease progression, intolerable toxicity, patient withdraw ICF or death.

Also known as: yiruike

gefitinib combined with apatinib

gefitinib single agent DRUG

Patients received Gefitinib 250mg q.d. orally until disease progression, intolerable toxicity or death.

Also known as: yiruike

gefitinib single agent

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Volunteered for attending the study, and signed informed consent form (ICF)to participate in the study.
• Cytologically and Histologically documented, locally advanced or recurrent or metastatic (stage IIIb, IIIc, IV) non-small cell lung cancer patients .
• EGFR mutation (exon 19 deletion or exon 21 L858R) with Bim deletion or low abundance for EGFR mutation.
• Age range: 18 years to 75 years.
• Patients must have measurable lesion according to the RECIST (version 1.1) criteria.
• Life expectancy of ≥ 12 weeks
• ECOG (Eastern Cooperative Oncology Group) performance status of ≤ 1.
• Patients hadn't received past system treatment, including cytotoxic drugs; For patients who have received adjuvant or neoadjuvant chemotherapy appears recurrence or metastasis more than 6 months from accepting the last dose of chemotherapy drugs
• Adequate organ function as defined by the following criteria:
• Bone marrow function: absolute neutrophil count ≥ 1,500,000,000/L and platelet count ≥100,000,000,000/L and hemoglobin ≥9g/dL.
• Liver function: Total bilirubin ≤ 1.5 ULN (upper limit of normal). AP (alkaline phosphatase), AST ( aspartate aminotransferase) and ALT (alanine transaminase) ≤ 3 ULN in the absence of liver metastases or up to 5 ULN in case of liver metastases.
• Renal function: creatinine clearance ≥ 60 ml/min. (based on modified Cockcroft-Gault formula).
• INR （international normalized ratio）≤ 1.5, and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 ULN.
• For all females of childbearing potential a negative serum/urine pregnancy test must be obtained within 48 hours before enrollment. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential.
• Fertile men and women must use effective contraception.

You may not qualify if:

• Histology confirmed for squamous carcinomas, including mixed gland scale cancer, small cell lung cancer.
• Poor controlled hypertension, it means systolic pressure ≥140 mmHg and/or diastolic pressure ≥90 mmHg after drug therapy.
• There are imaging evidence of tumor invading or closing to the pulmonary vessels (e.g., pulmonary artery, superior vena cava).
• Thrombosis in 6 months before enrollment, including pulmonary thrombosis or deep venous thrombosis., or patient had medical evidence or history of thrombosis or bleeding tendency regardless of the severity.
• Patients with medical history of hemoptysis (defined as about 2.5ml bright blood) 2 weeks before the enrollments.
• Proteinuria ≥++, or 24h proteinuria ≥1.0g.
• A uncontrolled clinical infection, activity, including but not limited to acute pneumonia.
• Patients with known liver disease: the hepatitis B virus (HBV) infection and hepatitis b virus DNA (HBV DNA) ≥ 500 copy number or ≥100 IU/ml; or more; or hepatitis C virus (HCV) infection; or liver cirrhosis, etc.
• Patients who are at risk of human immunodeficiency virus (HIV) or syphilis infection.
• Patients who have a difficulty in swallowing or drug absorption.
• There are diseases of alimentary canal such as active duodenal ulcer, the ulcerous colitis, intestinal obstruction or other conditions which can cause gastrointestinal bleeding or perforation in the investigator's opinion; or patient has a history of intestinal perforation, intestinal fistula.
• Evaluation of cardiac function: left ventricular ejection fraction \< 50% (echocardiography); Moderate or above disorders of mitral valve and tricuspid shut down;, serious/unstable angina or acute myocardial infarction coronary artery bypass surgery in 6 months before enrollment; patients with class 2 and above cardiac dysfunction according to New York heart association (NYHA) classification
• Stroke and transient ischemic in 12 months before enrollment.
• severe ulcer in the skin wound, trauma and mucosa or fractures have been not fully healed.
• Patients received CYP3A4 strong inhibitor and/or inducer in 2 weeks before enrollment; Patients received P-gp and breast cancer resistance protein (BCRP) substrates drug in 2 weeks before enrollment.

Sponsors & Collaborators

• Qilu Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Shanghai Pulmonary Hospital;

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Drug Therapy; apatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Caicun Zhou

  Shanghai Pulmonary Hospital, Shanghai, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caicun Zhou, MD

CONTACT

+8613301825532; caicunzhoudr@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2017
• First Posted: August 30, 2017
• Study Start: October 12, 2017
• Primary Completion: October 20, 2020
• Study Completion: December 30, 2021
• Last Updated: August 3, 2020

Record last verified: 2020-07

Locations

CN (1)