Clinical trial NCT01204307: Influence of Prior Chemotherapy on Clinical Benefit With Erlotinib in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer With or Without EGFR Gene Mutation
Official title: A Phase III Study to Investigate the Differential Influence of Prior Chemotherapy on the Efficacy of Erlotinib in Patients With Advanced Non-small Cell Lung Cancer (IIIB, IV) With or Without EGFR Gene Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Non-Squamous Non-Small Cell Lung Cancer
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
Collaborators: name: Taiwan Chest Disease Association
First posted: 2010-09-17
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare the differential influence of 1st line doublet chemotherapy containing Docetaxel versus Pemetrexed on clinical efficacy of Erlotinib as a second line therapy in patients with relapsed or progressed non-squamous NSCLC.

Detailed description: The clinical management of advanced non-small cell lung cancer (NSCLC) remains challenging. Initial therapies for advanced NSCLC with platinum-based regimens have shown consistent overall response rates of 30% to 40% with progression-free intervals of 4-5 months and 1-year survival rates of 35% to 40% \[1-3\]. First line doublet chemotherapy commonly used in daily practice includes Gemcitabine, vinorelbine, paclitaxel and docetaxel those have proven efficacy with platinum against best supportive care, prolonging survival for approximately 3 months. Recently, pemetrexed, a multi-target antifolate agent, has been introduced into the 1st line doublet chemotherapy with platinum-based regimen to have similar efficacy and a better safety profile compared to docetaxel or gemcitabine \[4\]. Although those agents seem to have equivalent efficacy, tolerability tends to be a concern for docetoxel.

Myelosuppression with the standard docetaxel schedule of 75 mg/m2 administered once every 3 weeks is extremely frequent and severe; neutropenia occurs in 54% to 67% of patients and febrile neutropenia occurs in 1.8% to 8.0% of patients \[5, 6\]. Moreover, non-hematologic toxicities, such as grade 3-4 asthenia (12% to 18%), and nausea and vomiting (1% to 3.6%), are not uncommon \[5, 6\]. To increase tolerability of docetaxel, alternative schedules have been extensively studied. Accumulating evidence suggests that a weekly schedule of docetaxel (35 mg/m2) reduces severe and febrile neutropenia without decreasing antitumor activity \[7-10\]. Nevertheless, no significant differences were observed for anemia, thrombocytopenia, and non-hematologic toxicity \[7\]. For the same reason, a lower dose of docetaxel (60 mg/m2 every 3 weeks) has been recommended in Japan \[11, 12\]. However, recent large scale trials with such a dose of docetaxel still revealed high incidences of grade 3 and 4 neutropenia (up to 82.9%) \[12-14\]. Different schedules of low dose docetaxel have not been studied, nor has a comparison been made between low dose docetaxel and the less toxic agent, pemetrexed.

Currently, the investigators have been following a schedule of weekly low dose docetaxel (30 mg/m2 on days 1 and 8 every 3 weeks; 60 mg/m2 accumulated dose for each cycle) at our hospital in an effort to achieve better tolerability (in press-chemotherapy 2010). The investigators therefore perform an exploratory study, by prospective analysis, to investigate the efficacy and toxicity of such a low dose docetaxel schedule compared to that of pemetrexed in patients with NSCLC who are chemotherapy naive.

Erlotinib, an orally-available epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI), significantly prolongs survival and produces significant symptom and quality-of-life benefits compared with best supportive care in unselected patients with relapsed non-small-cell lung cancer (NSCLC) \[15, 16\]. In a large, phase III, placebo-controlled study (BR.21), erlotinib produced a survival benefit across all patient sub-groups studied \[15\].

Eligibility criteria: Inclusion Criteria:

1. Patients \> 18 years, \<75 years old
2. Pathological confirmation of non-squamous NSCLC
3. Clinical stage IIIB or IV
4. Measurable tumor size by RECIST criteria
5. ECOG \<2
6. Adequate hematological laboratory parameters
7. Adequate hepatic, renal laboratory parameters

Exclusion Criteria:

1. Un-specified NSCLC
2. Prior therapy with any chemotherapy or EGFR TKI or monoclonal antibodies
3. Any unstable systemic disease (active infection, hypertension, unstable angina, CHF, liver cirrhosis, end stage renal failure etc., )
4. Nursing or pregnant mothers
5. Untreated Brain metastasis
6. ECOG\>2

Primary outcomes:
measure: Response rate to erlotinib with Docetaxel/cisplatin or Pemetrexed/cisplatin
timeFrame: 2-3 months
Secondary outcomes:
measure: Progression-free survival and overall survival after erlotinib treatment with 1st line Docetaxel/cisplatin or Pemetrexed/cisplatin.
timeFrame: 12-24 months
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital, Kaohsiung Branch
city: Taipei
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Taipei
country: Taiwan
facility: McKay Memorial Hospital
city: Taipei
country: Taiwan
facility: Shin Kong Wu Ho-Su Memorial Hospital
Study officials:
affiliation: Taiwan Chest Disease Association and Chang Gung Memorial Hospital
name: Han-Pin Kuo, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Feng PH, Lee KY, Chang YL, Chan YF, Kuo LW, Lin TY, Chung FT, Kuo CS, Yu CT, Lin SM, Wang CH, Chou CL, Huang CD, Kuo HP. CD14(+)S100A9(+) monocytic myeloid-derived suppressor cells and their clinical relevance in non-small cell lung cancer. Am J Respir Crit Care Med. 2012 Nov 15;186(10):1025-36. doi: 10.1164/rccm.201204-0636OC. Epub 2012 Sep 6.