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

NCT ID: NCT01204307

Last Updated: 2015-07-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2015-06-30

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].

Conditions

Advanced Non-Squamous Non-Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

docetaxel/cisplatin

The treatment schedule comprises a maximum of six 3-week treatment cycles consisting of weekly docetaxel (30 mg/m2) and cisplatin (37.5 mg/m2) for 2 consecutive weeks followed by a 1-week treatment-free period. The patients will be assessed after each cycle and a final assessment will be done after three and six cycles.

Group Type: EXPERIMENTAL

Docetaxel/cisplatin

Intervention Type: DRUG

The treatment schedule comprises a maximum of six 3-week treatment cycles consisting of weekly docetaxel (30 mg/m2) and cisplatin (37.5 mg/m2) for 2 consecutive weeks followed by a 1-week treatment-free period. The patients will be assessed after each cycle and a final assessment will be done after three and six cycles.

Pemetrexed/cisplatin

The patients are given pemetrexed (500 mg/m2 as a 10-min intravenous infusion) and cisplatin (75 mg/m2) on day 1 every 21 days. Dexamethasone (4 mg) is administered twice daily on the day before, the day of, and the day after each dose of pemetrexed. Oral folic acid supplementation (1000 mg) is administered daily, beginning approximately 2 weeks prior to the first dose of pemetrexed and continues until 3 weeks after treatment discontinuation. A 1000 mg vitamin B12 injection is administered intramuscularly approximately 1-2 weeks before the first dose of pemetrexed and is repeated approximately every 9 weeks until 3 weeks after therapy discontinuation.

Group Type: ACTIVE_COMPARATOR

Pemetrexed/cisplatin

Intervention Type: DRUG

The patients are given pemetrexed (500 mg/m2 as a 10-min intravenous infusion) and cisplatin (75 mg/m2) on day 1 every 21 days. Dexamethasone (4 mg) is administered twice daily on the day before, the day of, and the day after each dose of pemetrexed. Oral folic acid supplementation (1000 mg) is administered daily, beginning approximately 2 weeks prior to the first dose of pemetrexed and continues until 3 weeks after treatment discontinuation. A 1000 mg vitamin B12 injection is administered intramuscularly approximately 1-2 weeks before the first dose of pemetrexed and is repeated approximately every 9 weeks until 3 weeks after therapy discontinuation.

Interventions

Docetaxel/cisplatin

The treatment schedule comprises a maximum of six 3-week treatment cycles consisting of weekly docetaxel (30 mg/m2) and cisplatin (37.5 mg/m2) for 2 consecutive weeks followed by a 1-week treatment-free period. The patients will be assessed after each cycle and a final assessment will be done after three and six cycles.

Intervention Type: DRUG

Pemetrexed/cisplatin

The patients are given pemetrexed (500 mg/m2 as a 10-min intravenous infusion) and cisplatin (75 mg/m2) on day 1 every 21 days. Dexamethasone (4 mg) is administered twice daily on the day before, the day of, and the day after each dose of pemetrexed. Oral folic acid supplementation (1000 mg) is administered daily, beginning approximately 2 weeks prior to the first dose of pemetrexed and continues until 3 weeks after treatment discontinuation. A 1000 mg vitamin B12 injection is administered intramuscularly approximately 1-2 weeks before the first dose of pemetrexed and is repeated approximately every 9 weeks until 3 weeks after therapy discontinuation.

Intervention Type: DRUG

Other Intervention Names

Taxotere- made by Sanofi-Aventis.; Alimta- made by LiLy.

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Taiwan Chest Disease Association

OTHER

Sponsor Role: collaborator

Chang Gung Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Chung Fu-Tsai

Attending physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Han-Pin Kuo, MD, PhD

Role: STUDY_DIRECTOR

Taiwan Chest Disease Association and Chang Gung Memorial Hospital

Locations

Chang Gung Memorial Hospital

Taipei, Taipei, Taiwan

Chang Gung Memorial Hospital, Kaohsiung Branch

Kaohsiung City, , Taiwan

McKay Memorial Hospital

Taipei, , Taiwan

Shin Kong Wu Ho-Su Memorial Hospital

Taipei, , Taiwan

Countries

Taiwan

References

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.

Reference Type: DERIVED

PMID: 22955317 (View on PubMed)

Other Identifiers

99-1896C

Identifier Type: -

Identifier Source: org_study_id