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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2010 by Chang Gung Memorial Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Taiwan Chest Disease Association
Information provided by (Responsible Party):
Chung Fu-Tsai, Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier:
NCT01204307
First received: September 16, 2010
Last updated: March 8, 2012
Last verified: September 2010
  Purpose

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.


Condition Intervention Phase
Advanced Non-Squamous Non-Small Cell Lung Cancer
Drug: Docetaxel/cisplatin
Drug: Pemetrexed/cisplatin
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Chang Gung Memorial Hospital:

Primary Outcome Measures:
  • Response rate to erlotinib with Docetaxel/cisplatin or Pemetrexed/cisplatin [ Time Frame: 2-3 months ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Progression-free survival and overall survival after erlotinib treatment with 1st line Docetaxel/cisplatin or Pemetrexed/cisplatin. [ Time Frame: 12-24 months ] [ Designated as safety issue: Yes ]
    Erlotinib 150 mg daily will be given to patients who are in progression after 1st line cisplatin-base doublet chemotherapy. Treatment will continue until documented disease progression, or patient refusal to continue. The progression-free survival encompasses the time from the start date of the Erlotinib treatment to documented progression, or death from any cause. The Overall survival from each arm of treatment is calculated from the start date of the treatment to death or to the last follow-up visit.


Estimated Enrollment: 250
Study Start Date: January 2010
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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.
Other Name: Taxotere- made by Sanofi-Aventis.
Active Comparator: 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.
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.
Other Name: Alimta- made by LiLy.

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01204307

Contacts
Contact: Kang-Yuan Lee, MD, PhD +886-3-3281200 ext 8467 lee4949@ms41.hinet.net

Locations
Taiwan
Chang Gung Memorial Hospital, Kaohsiung Branch Recruiting
Kaohsiung, Taiwan
Contact: Sui-Liong Wong         
Principal Investigator: Sui-Liong Wong         
McKay Memorial Hospital Recruiting
Taipei, Taiwan
Contact: Chien-Liang Wu         
Principal Investigator: Chien-Liang Wu         
Shin Kong Wu Ho-Su Memorial Hospital Recruiting
Taipei, Taiwan
Contact: Shang-Jyh Kao         
Principal Investigator: Shang-Jyh Kao         
Chang Gung Memorial Hospital Recruiting
Taipei, Taiwan, 10507
Contact: Kang-Yuan Lee, MD, PhD    +886-3-3281200 ext 8467    lee4949@ms41.hinet.net   
Contact: Han-Pin Kuo, MD, PhD    +886-3-3281200 ext 8467    q8828@ms11.hinet.net   
Principal Investigator: Kang-Yuan Lee, MD, PhD         
Sub-Investigator: Fu-Tsai Chung, MD         
Sponsors and Collaborators
Chang Gung Memorial Hospital
Taiwan Chest Disease Association
Investigators
Study Director: Han-Pin Kuo, MD, PhD Taiwan Chest Disease Association and Chang Gung Memorial Hospital
  More Information

No publications provided by Chang Gung Memorial Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Chung Fu-Tsai, Attending physician, Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier: NCT01204307     History of Changes
Other Study ID Numbers: 99-1896C
Study First Received: September 16, 2010
Last Updated: March 8, 2012
Health Authority: Taiwan: Institutional Review Board

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Docetaxel
Pemetrexed
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on September 18, 2014