Intercalating and Maintenance Gefitinib in Combination With Chemotherapy for Advanced EGFR-mutant NSCLC

NCT02299765 | Terminated Phase 4 DMC

• 1 other identifier: ISSIRES0109
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

Study Title: Intercalating and maintenance Gefitinib in combination with chemotherapy (gemcitabine plus carboplatin) as first-line treatment for patients with advanced EGFR mutation-positive non-small cell lung cancer: A randomized, open-label, multiple-centre study. Target population-Treatment naive EGFR mutant-positive advanced NSCLC patients. Study Objectives - Primary Study Objective: To investigate whether intercalating and maintenance Gefitinib in combination with chemotherapy improve the Progression-Free Survival (PFS) vs. Gefitinib alone in advanced NSCLC with EGFR activating mutation. \- Secondary Study Objective： To evaluate whether intercalating and maintenance Gefitinib in combination with chemotherapy improve the Objective Response Rate (ORR), Disease control rate (DCR), Overall survival (OS), 2-year OS rate, QOL vs. Gefitinib alone. Evaluation the safety of Intercalating and Maintenance Gefitinib in combination with chemotherapy. \- Exploratory objective: PFS of arm A vs. PFS 1 + PFS 2 of arm B Dynamic biomarker analysis using blood sample a: The PFS 1 of arm B is the time from randomization to disease progression of 1st-line therapy or death from any cause, whichever occurs first. The PFS 2 of arm B is the time from the time of PFS 1 to disease progression of 2nd-line therapy or death from any cause, whichever occurs first. Study Design-Prospective, open-label, randomized, multi-center study.

Conditions

Non-small Cell Lung Cancer Metastatic; EGFR Activating Mutation

Keywords

Advanced Non-small Cell Lung Cancer (NSCLC); EGFR Mutation; gefitinib; chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression free survival - PFS

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to average 10 months

Secondary Outcomes (2)

• Objective Response Rate - ORR

  at day 42 of treatment

• Overall Survival - OS

  the time from randomization to death from any cause,assessed up to 2 years

Study Arms (2)

Arm A

EXPERIMENTAL

Four cycles gemcitabine(d1,8 ) + carboplatin (d1) + gefitinib (15-25), gefitinib 250mg/d from d15 of last cycle until disease progression. Gemcitabine=1000mg/m2;Carboplatin 5×AUC ; One cycle is 28 days

Drug: Gefitinib; Drug: gemcitabine; Drug: carboplatin

Arm B

ACTIVE COMPARATOR

Gefitinib 250mg/d until disease progression

Drug: Gefitinib

Interventions

Gefitinib DRUG

patients in arm A will be given gefitinib as target therapy

Also known as: Iressa

Arm A; Arm B

gemcitabine DRUG

patients in arm A will be given gemcitabine chemotherapy

Also known as: Gemza

Arm A

carboplatin DRUG

patients in arm A will be given carboplatin chemotherapy

Also known as: Carboplatin Injection

Arm A

Eligibility Criteria

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

You may qualify if:

• Patients between 18 and 75 years of age.
• Patients with histologically or cytologically diagnosed NSCLC,or patients with recurrent advanced NSCLC after surgery.
• Harboring activating mutation of EGFR,only including an exon 19 deletion or an exon 21 point mutation.
• Has at least one measureable lesion by RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• No prior systemic chemotherapy or targeted therapy for lung cancer before screening except neoadjuvant or adjuvant patients.
• Adequate organ function, including the following:
• Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥1.5 × 109/L,platelets ≥100 × 109/L,and hemoglobin ≥9 g/dL.
• Hepatic: bilirubin ≤1.5 times the upper limit of normal (× ULN),alkaline phosphatase (AP),aspartate transaminase (AST),and alanine transaminase (ALT) ≤3.0 × ULN (AP,AST and ALT ≤5 × ULN is acceptable if the liver has tumor involvement).
• Renal: calculated creatinine clearance (CrCl) ≥45 mL/minute based on the standard Cockcroft and Gault formula.
• Prior radiation therapy allowed to \<25% of the bone marrow. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed at least 4 weeks before study enrolment.
• Signed informed consent document on file.
• Estimated life expectancy of ≥12 weeks.
• Patient compliance and geographic proximity that allow adequate follow up.

You may not qualify if:

• Known severe hypersensitivity to gefitinib.
• Known brain metastasis unless asymptomatic brain metastasis(without neurotic symptoms and sign) and treated with surgery and/or radiation and stable without steroid treatment for at least 2 weeks prior to the first dose of study medication.
• Pleural effusion or pericardiac effusion that cannot be controlled by drainage or other procedures.
• Previous treatment with agents targeting the HER axis.
• Previous systemic antitumour treatment.
• The last regimen of neoadjuvant or adjuvant treatment for non-metastatic disease within 12 months of study treatment.
• EGFR Resistance mutation (+).
• Surgery undertaken less than 4 weeks before the study.
• 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.
• Second primary malignancy that is clinically detectable at the time of consideration for study enrolment.
• Past medical history of Interstitial Lung Disease(ILD),drug induced interstitial disease,radiation pneumonitis which required steroid treatment,or any evidence of clinically active ILD.
• Pre-existing idiopathic pulmonary fibrosis evidence by CT scan at baseline.
• Unwillingness to use contraception during the study, women who were pregnant or lactating.

Sponsors & Collaborators

• Sichuan University: lead
• AstraZeneca: collaborator

Study Sites (1)

China West Hospital

Chengdu, Sichuan, 610000, China

Location

Related Publications (19)

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MeSH Terms

Interventions

Gefitinib; Gemcitabine; Carboplatin

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Study Officials

• You Lu, MD

  Department of Thoracic Oncology, Cancer center, West China Hospital, Sichuan University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: November 18, 2014
• First Posted: November 24, 2014
• Study Start: December 1, 2014
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: November 27, 2017

Record last verified: 2017-11

Locations

CN (1)