TCL-1: Intercalated Combination of Chemotherapy and Tyrosine Kinase Inhibitors as First-line Treatment for Patients With Non-Small-Cell Lung Cancer

Sponsor

Qilu Hospital of Shandong University (Other)

Overall Status

Unknown status

CT.gov ID

NCT02031601

Collaborator

(none)

250

Enrollment

Location

Arms

Duration (Months)

5.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Small-Cell Lung Cancer	Drug: Erlotinib Drug: Gefitinib Drug: Icotinib Drug: Docetaxel Drug: Pemetrexed Drug: Platinum (cisplatin or carboplatin) Drug: Erlotinib Drug: Gefitinib Drug: Icotinib	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

250 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomised, Controlled Study Comparing Chemotherapy Plus Intercalated EGFR-Tyrosine Kinase Inhibitors Combination Therapy With EGFR-Tyrosine Kinase Inhibitors Alone Therapy as First-line Treatment for Patients With Non-Small-Cell Lung Cancer

Study Start Date :

Jan 1, 2014

Anticipated Primary Completion Date :

Dec 1, 2016

Anticipated Study Completion Date :

Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Combination therapy 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)	Drug: Erlotinib 150mg po once a day on days 2-15 of each 3 week cycle for 4 cycles; then continue to receive erlotinib150mg po once a day daily until progression Other Names: Tarceva Drug: Gefitinib 250mg po once a day on days 2-15 of each 3 week cycle for 4 cycles; then continue to receive gefitinib 250mg po once a day daily until progression Other Names: Iressa Drug: Icotinib 125mg po three time a day on days 2-15 of each 3 week cycle for 4 cycles; then continue to receive icotinib 125mg po three time a day daily until progression Other Names: Conmana Drug: Docetaxel 75 mg/m2 ivgtt on days 1 of each 3 week cycle for 4 cycles Drug: Pemetrexed 500 mg/m2 ivgtt on days 1 of each 3 week cycle for 4 cycles Drug: Platinum (cisplatin or carboplatin) cisplatin -- 75mg/m2 ivgtt on day 1 of each 3 week cycle for 4 cycles or carboplatin -- 5 x AUC ivgtt on day 1 of each 3 week cycle for 4 cycles
Other: TKI alone therapy Interventions: Drug: Erlotinib [Tarceva] or Gefitinib [Iressa] or Icotinib [Conmana]	Drug: Erlotinib 150mg po once a day daily until disease progression Other Names: Tarceva Drug: Gefitinib 250mg po once a day daily until disease progression Other Names: Iressa Drug: Icotinib 125mg po three times a day daily until disease progression Other Names: Conmana

Arm

Intervention/Treatment

Experimental: Combination therapy

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)

Drug: Erlotinib

150mg po once a day on days 2-15 of each 3 week cycle for 4 cycles; then continue to receive erlotinib150mg po once a day daily until progression

Other Names:

Tarceva

Drug: Gefitinib

250mg po once a day on days 2-15 of each 3 week cycle for 4 cycles; then continue to receive gefitinib 250mg po once a day daily until progression

Other Names:

Iressa

Drug: Icotinib

125mg po three time a day on days 2-15 of each 3 week cycle for 4 cycles; then continue to receive icotinib 125mg po three time a day daily until progression

Other Names:

Conmana

Drug: Docetaxel

75 mg/m2 ivgtt on days 1 of each 3 week cycle for 4 cycles

Drug: Pemetrexed

500 mg/m2 ivgtt on days 1 of each 3 week cycle for 4 cycles

Drug: Platinum (cisplatin or carboplatin)

cisplatin -- 75mg/m2 ivgtt on day 1 of each 3 week cycle for 4 cycles or carboplatin -- 5 x AUC ivgtt on day 1 of each 3 week cycle for 4 cycles

Other: TKI alone therapy

Interventions: Drug: Erlotinib [Tarceva] or Gefitinib [Iressa] or Icotinib [Conmana]

Drug: Erlotinib

150mg po once a day daily until disease progression

Other Names:

Tarceva

Drug: Gefitinib

250mg po once a day daily until disease progression

Other Names:

Iressa

Drug: Icotinib

125mg po three times a day daily until disease progression

Other Names:

Conmana

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.