Erlotinib Versus Gemcitabine/Carboplatin in Chemo-naive Stage IIIB/IV Non-Small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor (EGFR) Exon 19 or 21 Mutation (ML20981)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2009 by Tongji University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Sun Yat-sen University
Shanghai Chest Hospital
RenJi Hospital
Guangdong Provincial People's Hospital
Peking Union Medical College Hospital
Information provided by:
Tongji University
ClinicalTrials.gov Identifier:
NCT00874419
First received: April 1, 2009
Last updated: May 18, 2011
Last verified: August 2009
  Purpose

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) such as erlotinib have proved effective in second or third line therapy for advanced non-small cell lung cancer(NSCLC).It is well tolerated without the side effects usually associated with chemotherapy. The mutations in EGFR exons 19 or 21 have been reported to be associated with efficacy of EGFR TKIs.Based on the encouraging preliminary results from the Spanish lung cancer group' prospective study reported that the efficacy of Tarceva as first line treatment for metastatic NSCLC patients with EGFR mutation would delay disease progression,prolong overall survival and be well tolerated, medium Progression-free survival(PFS) was around 12 months and OS reach 24 months,our study is designed to compare PFS between the patients with mutant EGFR treated by gemcitabine/carboplatin and those by erlotinib in the first-line setting. We assumed 11 months of PFS on Tarceva arm versus 6 months on chemotherapy arm with a=0.025(alpha-spend for an interim analysis), 80% power and 12 months enrolment period, 12 months FU duration to calculate the sample size. The sample size is 69 pairs. Considering about 10% drop-out rate, the final sample size is 152 patients.So, chemo-naive staged IIIb/IV patients with EGFR mutations in exon 19 or 21 will be enrolled into this open-label, randomized,multicenter phase III study.


Condition Intervention Phase
Non-small Cell Lung Cancer
Drug: erlotinib
Drug: gemcitabine/carboplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-label, Multi-center Phase III Study of Erlotinib Versus Gemcitabine/Carboplatin in Chemo-naive Stage IIIB/IV Non-Small Cell Lung Cancer Patients With EGFR Exon 19 or 21 Mutation (Optimal)

Resource links provided by NLM:


Further study details as provided by Tongji University:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • OS [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • ORR [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Time to Progression [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • lung cancer symptoms and health-related quality of life (HRQoL) [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • explore the biological markers (tumor tissue) [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 152
Study Start Date: August 2008
Estimated Study Completion Date: July 2011
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: erlotinib
Arm 1 receive erlotinib 150 mg oral, once a day until progression or unacceptable toxicity
Drug: erlotinib
erlotinib 150 mg oral, once a day
Other Name: Tarceva
Active Comparator: gemcitabine/carboplatin
gemcitabine 1000mg/m2 on d1,8 with carboplatin AUC=5 on d1 intravenously, every 3 weeks, up to 4 cycles
Drug: gemcitabine/carboplatin
gemcitabine 1000mg/m2 on d1,8 with carboplatin AUC=5 on d1 intravenously, every 3 weeks, up to 4 cycles
Other Name: Gemzar

Detailed Description:

Primary Outcome Measures:

Progression-free survival(PFS) Secondary Outcome Measures: Overall response rate(ORR), overall survival(OS), quality of life(QOL),etc.

Estimated Enrollment: 160 Study Start Date: August 2008 Estimated Study Completion Date: August 2010

The patients will be randomized into the following two arms:

Arm A: erlotinib 150mg once per day up to disease progression or intolerable toxicity.

Arm B: Gemcitabine (1000mg/m2, IV,d1 and d8) plus Carboplatin (AUC=5, IV d1) repeated every 3 weeks up to 4 cycles.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Stage IIIB (cytological confirmed with malignant pleural effusion or pericardial effusion) or histopathological or cytological confirmed stage IV NSCLC or relapsed after complete resection .
  2. EGFR exon19 deletions or exon 21 L858R mutation by the DNA direct PCR sequencing using fresh tumor sample or paraffin embed tumor sample.
  3. Measurable lesions as defined by RECIST criteria .
  4. Palliative radiotherapy allowed if it was finished 3 weeks after the first drug administration, but the target lesions should not be included in the radiotherapy field.
  5. Patients with operation are allowed if the operation is 4 weeks before the first drug administration
  6. Men or women of at least 18 years of age.
  7. ECOG Performance status of 0 to 2.
  8. Estimated life expectancy of at least 12 weeks.
  9. Patient compliance and geographic proximity that allow adequate follow-up.
  10. Adequate organ function tested 7 days before the first drug administration:

    hemoglobin ≥9 g/dL,absolute neutrophil count (ANC) ≥1.5*109/L, platelets ≥100 *109/L,bilirubin ≤1.5ULN, alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 upper limited number(ULN) (AP, AST, ALT ≤5ULN is acceptable if liver has tumor involvement).INR≤1.5, APTT in the normal range( 1.2DLN-1.2ULN),creatinine ≤1.5ULN.

  11. Informed consent from the patient.

Exclusion Criteria:

  1. Have received systemic anti-cancer therapy, including Cytotoxic drugs, targeted therapy, experimental treatment, adjuvant or neo-adjuvant therapy(except the disease relapse 6 months after the final drug)
  2. Wild type EGFR.
  3. Uncontrolled pericardial or pleural effusions prior to study entry.
  4. History of cardiovascular disease: Congestive Heart Failure > grade II in NYHA. Unstable angina patients (have angina symptoms in rest) or a new occurrence of angina (began in the last 3 months) or myocardial infarction happens in the last 6 months
  5. Brain metastasis (controlled brain metastasis and steroid free need is excluded).
  6. HIV infection
  7. Active infection, >grade 2 in Common Terminology Criteria for Adverse Events(CTCAE) version 3.
  8. A history of operation or serious traumatic 3 weeks before the first drug administration
  9. Patient with other malignant tumor except NSCLC 5 years previous to study entry. Excluding cervical carcinoma in situ, cured basal cell carcinoma, bladder epithelial tumor [including Ta and Tis]
  10. Mixed with small cell lung cancer
  11. Unable to swallow drugs.
  12. Malabsorption
  13. Pregnant or child breast feeding women
  14. Childbearing patients will not use a reliable method of contraception before the study entry, during process of the study and within 30 days after discontinuation of the study. Reliable contraceptive methods will be determined by principal investigator or a designated officer.
  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: NCT00874419

Locations
China
Medical Department, Shanghai Pulmonary Hospital
Shanghai, China, 200433
Sponsors and Collaborators
Tongji University
Sun Yat-sen University
Shanghai Chest Hospital
RenJi Hospital
Guangdong Provincial People's Hospital
Peking Union Medical College Hospital
Investigators
Principal Investigator: Caicun Zhou, MD & PhD Tongji University
  More Information

No publications provided by Tongji University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Caicun Zhou, Tongji University Affiliated Shanghai Pulmonary Hospital
ClinicalTrials.gov Identifier: NCT00874419     History of Changes
Other Study ID Numbers: ML20981
Study First Received: April 1, 2009
Last Updated: May 18, 2011
Health Authority: China: Food and Drug Administration

Keywords provided by Tongji University:
EGFR mutation
EGFR-TKI
Chemotherapy

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gemcitabine
Erlotinib
Carboplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014