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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

Phase 3
18 Years
75 Years
Open (Enrolling)
Advanced Non-Squamous Non-Small Cell Lung Cancer

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Trial Information

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

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].

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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate to erlotinib with Docetaxel/cisplatin or Pemetrexed/cisplatin

Outcome Description:

Eligible patients will be randomized to receive 1st line chemotherapy with either Docetaxel (60mg/m2)/Cisplatin (75mg/m2) or Pemetrexed (500mg/m2)/Cisplatin (75mg/m2) for 4-6 cycles. Patients will be followed up without any maintenance treatment after 4-6 cycles of chemotherapy. Once patients are found tumor relapse or in progression, all the patients will be prescribed Erlotinib 150 mg/day until disease progression, unacceptable toxicity or death. Patients will be followed up every 2-3 months for their responsive rate.

Outcome Time Frame:

2-3 months

Safety Issue:


Principal Investigator

Han-Pin Kuo, MD, PhD

Investigator Role:

Study Director

Investigator Affiliation:

Taiwan Chest Disease Association and Chang Gung Memorial Hospital


Taiwan: Institutional Review Board

Study ID:




Start Date:

January 2010

Completion Date:

December 2012

Related Keywords:

  • Advanced Non-squamous Non-Small Cell Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms