Intercalated Combination of Chemotherapy and Tyrosine Kinase Inhibitors as First-line Treatment for Patients With Non-Small-Cell Lung Cancer

Phase 4

• Conditions: Non-Small-Cell Lung Cancer
• Interventions: Drug: Erlotinib; Drug: Gefitinib; Drug: Icotinib; Drug: Docetaxel; Drug: Pemetrexed; Drug: Platinum (cisplatin or carboplatin)

• Registration Number: NCT02031601
• Lead Sponsor: Qilu Hospital of Shandong University

Brief Summary

Objective: To compare the efficacy and safety of chemotherapy plus intercalated EGFR-tyrosine kinase inhibitors (TKI) combination therapy with TKI alone therapy as first-line treatment for patients with non-small-cell lung cancer (NSCLC).

Methods: Patients with untreated, stage IIIB/IV, EGFR mutation-positive NSCLC will be randomly assigned to combination therapy group (receiving four cycles of docetaxel or pemetrexed (on day 1) plus platinum (on day 1) with intercalated TKI (gefitinib, erlotinib or Icotinib, on day 2-15) every 3 weeks) or TKI alone therapy (gefitinib, erlotinib or Icotinib, daily). All patients were continued to receive TKI until progression or unacceptable to toxicity or death. The primary endpoint was progression-free survivial (PFS).

Expected results: PFS of combination therapy group will be prolonged to nineteen months while PFS of TKI alone therapy group is ten months. Overall survival (OS) of combination therapy group will be prolonged to 36 months while OS of TKI alone therapy group is 26 months.

Hypothesis: Platinum-based chemotherapy plus intercalated TKI combination therapy as first-line treatment will prolong PFS and OS for patients with NSCLC.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-01
• Study First Submitted: 2014-01-02
• Study First Submitted QC: 2014-01-08
• Study First Posted: 2014-01-09
• Status Verified: 2015-11
• Last Update Submitted: 2016-03-28
• Last Update Posted: 2016-03-29
• Primary Completion: 2016-12
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

• Adult patients, >=18 years of age;
• Advanced (stage IIIB/IV) non-small-cell lung cancer;
• Although stageⅠ-ⅢA, have contraindications to surgery;
• EGFR mutation-positive (EGFR exon-18, exon-19 or exon-21);
• Measurable disease;
• ECOG Performance Status 0 or 1 or 2.

Exclusion Criteria

• Wild-type EGFR;
• Prior exposure to agents directed at the HER axis;
• Prior chemotherapy or systemic anti-tumor therapy after advanced disease;
• Unstable systemic disease;
• Any other malignancy within last 5 years, except cured basal cell cancer of skin or cured cancer in situ of cervix;
• Brain metastasis or spinal cord compression.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Combination therapy	Platinum (cisplatin or carboplatin)	Interventions: Drug: Erlotinib \[Tarceva\] or Gefitinib \[Iressa\] or Icotinib \[Conmana\] plus Drug: Docetaxel for patients of lung squamous cell carcinoma; Pemetrexed for patients of lung adenocarcinoma plus Drug: Platinum (cisplatin or carboplatin)
Combination therapy	Gefitinib	Interventions: Drug: Erlotinib \[Tarceva\] or Gefitinib \[Iressa\] or Icotinib \[Conmana\] plus Drug: Docetaxel for patients of lung squamous cell carcinoma; Pemetrexed for patients of lung adenocarcinoma plus Drug: Platinum (cisplatin or carboplatin)
Combination therapy	Erlotinib	Interventions: Drug: Erlotinib \[Tarceva\] or Gefitinib \[Iressa\] or Icotinib \[Conmana\] plus Drug: Docetaxel for patients of lung squamous cell carcinoma; Pemetrexed for patients of lung adenocarcinoma plus Drug: Platinum (cisplatin or carboplatin)
Combination therapy	Icotinib	Interventions: Drug: Erlotinib \[Tarceva\] or Gefitinib \[Iressa\] or Icotinib \[Conmana\] plus Drug: Docetaxel for patients of lung squamous cell carcinoma; Pemetrexed for patients of lung adenocarcinoma plus Drug: Platinum (cisplatin or carboplatin)
Combination therapy	Pemetrexed	Interventions: Drug: Erlotinib \[Tarceva\] or Gefitinib \[Iressa\] or Icotinib \[Conmana\] plus Drug: Docetaxel for patients of lung squamous cell carcinoma; Pemetrexed for patients of lung adenocarcinoma plus Drug: Platinum (cisplatin or carboplatin)
Combination therapy	Docetaxel	Interventions: Drug: Erlotinib \[Tarceva\] or Gefitinib \[Iressa\] or Icotinib \[Conmana\] plus Drug: Docetaxel for patients of lung squamous cell carcinoma; Pemetrexed for patients of lung adenocarcinoma plus Drug: Platinum (cisplatin or carboplatin)
TKI alone therapy	Erlotinib	Interventions: Drug: Erlotinib \[Tarceva\] or Gefitinib \[Iressa\] or Icotinib \[Conmana\]
TKI alone therapy	Gefitinib	Interventions: Drug: Erlotinib \[Tarceva\] or Gefitinib \[Iressa\] or Icotinib \[Conmana\]
TKI alone therapy	Icotinib	Interventions: Drug: Erlotinib \[Tarceva\] or Gefitinib \[Iressa\] or Icotinib \[Conmana\]

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	8 weeks	Progression-free survival (PFS) is defined to be the time from randomization to progression of disease or death, whichever occurs first. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Secondary Outcome Measures

Name	Time	Method
Time to progression	8 weeks
Clinical benefit rate	8 weeks
Objective response rate	8 weeks
Overall survival (OS)	8 weeks
Adverse Events (AEs), Serious Adverse Events (SAEs), laboratory data	4 weeks
Duration of response	8 weeks

Trial Locations

Locations (1)

Yu Li; 🇨🇳 Jinan, Shandong, China