Gefitinib Combined With Chemotherapy or Antiangiogensis in Patients With Bim Deletion or Low EGFR Mutation Abundance

NCT02930954 | Unknown Phase 2 DMC

• 1 other identifier: FK1408
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm phase II clinical trial, which aims to evaluate the effectiveness of combination of gefitinib and doublet chemotherapy or antiangiogenesis in advanced non-small cell lung cancer patients with EGFR activating mutation, accompanied with Bim deletion or low activating EGFR mutation abundance.

Conditions

Non-small-cell Lung Cancer

Keywords

NSCLC, EGFR, Bim, mutation abundance

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  From start of anti-cancer therapy untill progression or death

  8 weeks

Secondary Outcomes (3)

• overall survival

  36 months

• side effect

  8 weeks

• quality of life

  24 months

Study Arms (3)

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

Gefitinib combined with chemotherapy

EXPERIMENTAL

Gefitinib 250mg Qd combined with pemetrexed or gemcitabine plus carboplatin: Pemetrexed (500mg/m²day 1 intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days, Gemcitabine (1000 mg/m² days 1,d8, intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days

Drug: Gefitinib; Drug: pemetrexed or gemcitabine plus carboplatin,

Gefitinib combined with antiangiogenesis

EXPERIMENTAL

Gefetinib 250mg Qd combined with bevacizumab 7.5mg/kg per 21 days

Drug: Gefitinib; Drug: bevacizumab

Interventions

Gefitinib DRUG

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

Also known as: Iressa

Gefitinib combined with antiangiogenesis; Gefitinib combined with chemotherapy; Gefitinib single agent

pemetrexed or gemcitabine plus carboplatin, DRUG

doublet chemotherapy with pemetrexed or gemcitabine plus carboplatin per 3 weeks

Also known as: Alimita or Gimza

Gefitinib combined with chemotherapy

bevacizumab DRUG

bevacizumab 7.5mg/kg intravenously per 3 weeks

Gefitinib combined with antiangiogenesis

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically documented, locally advanced or recurrent (stage IIIb and not amenable to combined modality treatment) or metastatic (stage IV) non-small cell lung cancer, anti-cancer treatment naiive
• EGFR exon 19 deletion or exon 21 L858R.
• Bim deletion by realtime PCR, or low abundance for EGFR mutation, for 19Del less than 4.9%, for L858R less than 9.5%.
• ECOG performance status of ≤ 1.
• Patients must have measurable disease according to the RECIST (version 1.1) criteria.
• Life expectancy of at least 12 weeks
• Written (signed) informed Consent to participate in the study.
• Adequate organ function as defined by the following criteria:
• Liver function: SGOT (AST) and SGPT (ALT) ≤ 2.5 X ULN in the absence of liver metastases or up to 5 X ULN in case of liver metastases. Total bilirubin ≤ 1.5ULN.
• Bone marrow function: Granulocyte count ≥ 1,500/mm3 and platelet count ≥100,000/mm3 and hemoglobin ≥90g/dl.
• Renal function: serum creatinine ≤ 1.5 ULN or creatinine clearance ≥ 60 ml/min. (based on modified Cockcroft-Gault formula).
• 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.

You may not qualify if:

• Patients with prior chemotherapy or systemic anti-cancer therapy including target therapy targeting HER family members (such as erlotinib, gefitinib, cetuximab, trastuzumab, etc). Previous adjuvant or neo-adjuvant treatment for non-metastatic disease is permitted if completed ≥ 6 months before the enrollments.
• Patients with history of any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer).
• Patients who have brain metastasis or spinal cord compression. It is permitted if the patient has been treated with surgery and/or radiation with evidence of stable disease for at least 4 weeks.
• Patients who are at risk (in the investigator's opinion) of transmitting human immunodeficiency virus (HIV) through blood or other body fluids.
• lactating women
• Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.
• Unwilling to write informed consent to participate in the study or unwilling to receive follow-up
• Tumor invade big vessels or close to big vessels (less than 5mm)
• Obvious cavity or necrosis formed in the tumor, Uncontrolled hypertension, Myocardial ischemia or infarction more than stage II, cardiac insufficiency. Abnormal coagulation (INR\>1.5 or PT\>ULN+4, or APTT\>1.5 ULN), bleeding tendency or receiving coagulation therapy
• Hemoptysis, more than 2.5ml daily
• Thrombosis in 12 months, including pulmonary thrombosis, stoke, or deep venous thrombosis.
• Unhealed bone fracture or wound for long time

Sponsors & Collaborators

• Caicun Zhou: lead

Study Sites (1)

Department of Oncology, Shanghai pulmonary hospital

Shanghai, 200433, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Gefitinib; Pemetrexed; Gemcitabine; Carboplatin; Bevacizumab

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)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Caicun Zhou, MD,PhD

  Shanghai Pulmonary Hospital, Tongji University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caicun Zhou, MD,PhD

CONTACT

86-21-65115006; caicunzhoudr@163.com

shengxiang Ren, MD,PhD

CONTACT

86-21-65115006; harry_ren@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, doctor

Study Record Dates

• First Submitted: October 10, 2016
• First Posted: October 12, 2016
• Study Start: November 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: October 13, 2016

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)