Description:
Stage IIIA NSCLC represents a relatively heterogeneous group of pts with ipsilateral
mediastinal (N2) lymph node involvement. The relative roles of treatment modalities are not
clearly defined. Concurrent chemoradiation therapy remains an important treatment for stage
IIIA disease, but its treatment-related life threatening toxicity limits its use. The EGFR
tyrosine kinase inhibitor (TKI) may provide a dramatic response in pts with pulmonary
adenocarcinoma carrying EGFR activating mutations in the metastatic setting. In the OPTIMAL
study, first-line erlotinib versus carboplatin/GEM in advanced NSCLC pts with EGFR activating
mutations, the primary analysis showed significantly prolonged progressive free survival
(PFS) was with erlotinib vs carboplatin/GEM (p<0.0001). The aim of this study is to
investigate the efficacy and safety of erlotinib versus GEM plus cisplatin (GC) as
neoadjuvant treatment in pts with stage IIIA-N2 NSCLC with EGFR activating mutations and to
explore a new treatment strategy for this subset.
Title
- Brief Title: Erlotinib Versus Gemcitabine/Cisplatin as (Neo)Adjuvant Treatment in Non-small Cell Lung Cancer
- Official Title: A National, Multi Center, Randomized, Open-label, Phase II Trial of Erlotinib Versus Combination of GC as (Neo)Adjuvant Treatment in Stage IIIA-N2 NSCLC With Sensitizing EGFR Mutation in Exon 19 or 21(EMERGING)
Clinical Trial IDs
- ORG STUDY ID:
CTONG 1103
- SECONDARY ID:
ML25304
- NCT ID:
NCT01407822
- NCT ALIAS:
NCT01392404
Conditions
- Non-small Cell Lung Cancer
Interventions
Drug | Synonyms | Arms |
---|
Erlotinib | Tarceva | Erlotinib arm |
Gemcitabine/cisplatin | Gemzar/cisplatin | Chemo arm |
Purpose
Stage IIIA NSCLC represents a relatively heterogeneous group of pts with ipsilateral
mediastinal (N2) lymph node involvement. The relative roles of treatment modalities are not
clearly defined. Concurrent chemoradiation therapy remains an important treatment for stage
IIIA disease, but its treatment-related life threatening toxicity limits its use. The EGFR
tyrosine kinase inhibitor (TKI) may provide a dramatic response in pts with pulmonary
adenocarcinoma carrying EGFR activating mutations in the metastatic setting. In the OPTIMAL
study, first-line erlotinib versus carboplatin/GEM in advanced NSCLC pts with EGFR activating
mutations, the primary analysis showed significantly prolonged progressive free survival
(PFS) was with erlotinib vs carboplatin/GEM (p<0.0001). The aim of this study is to
investigate the efficacy and safety of erlotinib versus GEM plus cisplatin (GC) as
neoadjuvant treatment in pts with stage IIIA-N2 NSCLC with EGFR activating mutations and to
explore a new treatment strategy for this subset.
Detailed Description
Concurrent Chemoradiation therapy remain the standard treatment for stage IIIA disease, but
its treatment-related life threaten toxicity limit its use for those pts.
Tarceva monotherapy have been demonstrated a significant improvement in overall survival and
disease progression free survival when used for the treatment of patients with metastatic
NSCLC, after failure of at least one prior chemotherapy regimen. It is well tolerated without
the side effects usually associated with chemotherapy.
Based on the encouraging results reported from the SLCG phase II study reported the efficacy
of Tarceva as first line treatment for metastatic NSCLC with EGFR mutation patients would
prolong overall survival, delay disease progression and be well tolerated, mOS reached 27
months, ORR reached 71%. Besides, with different mechanism and more tolerable than chemo,
Tarceva may provide an important treatment alternative for local advanced pts with EGFR
mutation.
In IPASS study (gefitinib or carboplatin/paclitaxel in pulmonary adenocarcinoma as first line
treatment), the subgroup of 261 patients who were positive for the epidermal growth factor
receptor gene (EGFR) mutation, progression-free survival was significantly longer among those
who received gefitinib than among those who received carboplatin-paclitaxel (hazard ratio for
progression or death, 0.48; 95% CI, 0.36 to 0.64; P<0.001).
In OPTIMAL study (first-line erlotinib versus carboplatin/gemcitabine in Chinese advanced
NSCLC patients with EGFR activating mutations), the primary analysis showed PFS was
significantly prolonged with erlotinib vs carboplatin/paclitaxel(13.1months vs 4.6 months, HR
0.16 ; p<0.0001). The objective response rate was significantly improved with erlotinib vs
carboplatin/paclitaxel (83% vs 36%, p=0.0000), as was the disease control rate (CR + PR + SD;
96 vs 82%; p=0.002).
The aim of this study is to investigate the efficacy and safety of Tarceva versus combination
of Gemcitabine plus Cisplatin as neoadjuvant treatment in patients with stage IIIA- N2 NSCLC
with EGFR activating mutation in exon 19 or 21.
Trial Arms
Name | Type | Description | Interventions |
---|
Erlotinib arm | Experimental | In the neo-adjuvant treatment phase, erlotinib 150 mg/day taken orally for 6 weeks(42 days).In the post-surgery phase, erlotinib 150mg/day taken orally for 1 year or till disease progression or unacceptable toxicity. | |
Chemo arm | Active Comparator | In the neo-adjuvant treatment phase, patient will receive gemcitabine 1250mg/m2 IV on day 1 and day 8, and cisplatin 75mg/m2 on day 1 of a 3-week schedule for 2 cycles. In the post-surgery phase, Gemcitabine 1250mg/m2 IV on day 1 and day 8, and cisplatin 75mg/m2 on day 1 of a 3-week schedule for 2 cycles or till disease progression or unacceptable toxicity. | |
Eligibility Criteria
Inclusion Criteria:
- Written informed consent provided.
- Males or females aged ≥18 years.
- Able to comply with the required protocol and follow-up procedures, and able to
receive oral medications.
- Pathologically diagnosed of non-small cell lung cancer.
- Diagnosed as stage IIIA- N2.The diagnosis standard of N2 is as below: Pts with
resectable stage IIIA-N2 NSCLC confirmed by mediastinoscopy or EBUS or PET/CT.
- EGFR activating mutation in exon 19 or 21 by the biopsy of primary tumor or N2 lymph
node.
- Measurable disease must be characterized according to RECIST 1.1 criteria.
- Measurable lesions are defined as those that can be accurately measured in at least
one dimension (longest diameter to be recorded) as ≥ 10mm by spiral CT or MRI scan.
The measurable criteria of lymph node is the short axis ≥ 15 mm.
- ECOG performance status 0-1.
- Life expectancy ≥12 weeks.
- Adequate hematological function:Absolute neutrophil count (ANC) ≥1.5 x 109/L, and
Platelet count ≥100 x 109/L, and Hemoglobin ≥9 g/dL (may be transfused to maintain or
exceed this level).
- Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN);Aspartate
aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN in subjects without
liver metastases; ≤ 5 x ULN in subjects with liver metastases.
- Adequate renal function:Serum creatinine ≤ 1.25 x ULN, and creatinine clearance ≥ 60
ml/min.
- Female subjects should not be pregnant or breast-feeding.
Exclusion Criteria:
- Patients with prior exposure to agents directed at the HER axis (e.g. erlotinib,
gefitinib, cetuximab, trastuzumab).
- Patients with prior chemotherapy or therapy with systemic anti-tumour therapy (e.g.
monoclonal antibody therapy).
- Resection of primary malignancy.
- EGFR mutation (exon 19 or 21) negative or unknown.
- Uncontrolled central nervous system (CNS) metastasis.
- History of another malignancy in the last 5 years with the exception of the
following:Other malignancies cured by surgery alone and having a continuous
disease-free interval of 5 years are permitted; Cured basal cell carcinoma of the skin
and cured in situ carcinoma of the uterine cervix are permitted.
- Any unstable systemic disease (including active infection, uncontrolled hypertension,
unstable angina, congestive heart failure, myocardial infarction within the previous
year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic
disease).
- Known hypersensitivity to Tarceva or gemcitabine or cisplatin.
- Eye inflammation or eye infection not fully treated or conditions predisposing the
subject to this.
- Evidence of any other disease, neurological or metabolic dysfunction, physical
examination or laboratory finding giving reasonable suspicion of a disease or
condition that contraindicated the use of an investigational drug or puts the subject
at high risk for treatment-related complications.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | The objective response rate (ORR) in neoadjuvant treatment |
Time Frame: | Tumor response will be evaluated after 6 weeks of induction treatment (during day 43 to day 49). |
Safety Issue: | |
Description: | To evaluate objective response rate (ORR) of Erlotinib versus combination of Gemcitabine plus Cisplatin as neoadjuvant treatment for stage IIIA- N2 NSCLC with EGFR activating mutation in exon 19 or 21. |
Secondary Outcome Measures
Measure: | Complete resection rate |
Time Frame: | The patients considered to be technically resectable will undergo resection. Lymph node downstage rate is depended on the pathology dignosis after surgery, an expected average of 8 weeks from randomization. |
Safety Issue: | |
Description: | To evaluate radical resection rate of two groups. |
Measure: | Pathological complete response (pCR) rate |
Time Frame: | The patients considered to be technically resectable will undergo resection. Lymph node downstage rate is depended on the pathology dignosis after surgery, an expected average of 8 weeks from randomization. |
Safety Issue: | |
Description: | To evaluate the pathological complete response (pCR) rate of two groups. |
Measure: | Progression free survival(PFS) |
Time Frame: | Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan (ECT) every 12 months for up to 2 years. |
Safety Issue: | |
Description: | To evaluate Progressive Free Survival (PFS) of two groups. |
Measure: | 3 year overall survival (OS) rate |
Time Frame: | Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan (ECT) every 12 months for up to 2 years. |
Safety Issue: | |
Description: | To evaluate the 3 year overall survival (OS) rate of two groups.The third year after surgery is survival follow-up. |
Measure: | Number of Participants with Adverse Events |
Time Frame: | During the neoadjuvant and adjuvant period, an expected average of 1 years from randomization. |
Safety Issue: | |
Description: | To evaluate the safety profile(Number of Participants with Adverse Events) of two group. |
Measure: | Quality of Life (QOL) |
Time Frame: | During the neo-adjuvant treatment phase(1-42 days), surgery treatment phase and adjuvant phase, , an expected average of 1 years from randomization. |
Safety Issue: | |
Description: | To evaluate the Quality of Life (QOL) of two group |
Details
Phase: | Phase 2/Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Guangdong Association of Clinical Trials |
Trial Keywords
- Lung cancer
- IIIA-N2
- Neo-adjuvant treatment
- EGFR mutations
- Tyrosine kinase inhibitor
Last Updated
September 11, 2018