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

NCT00874419 | Completed Phase 3 DMC

• 1 other identifier: ML20981
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer

Keywords

EGFR mutation; EGFR-TKI; Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  12 months

Secondary Outcomes (5)

• OS

  24 months

• ORR

  24 months

• Time to Progression

  24 months

• lung cancer symptoms and health-related quality of life (HRQoL)

  24 months

• explore the biological markers (tumor tissue)

  24 months

Study Arms (2)

erlotinib

EXPERIMENTAL

Arm 1 receive erlotinib 150 mg oral, once a day until progression or unacceptable toxicity

Drug: erlotinib

gemcitabine/carboplatin

ACTIVE COMPARATOR

gemcitabine 1000mg/m2 on d1,8 with carboplatin AUC=5 on d1 intravenously, every 3 weeks, up to 4 cycles

Drug: gemcitabine/carboplatin

Interventions

erlotinib DRUG

erlotinib 150 mg oral, once a day

Also known as: Tarceva

erlotinib

gemcitabine/carboplatin DRUG

gemcitabine 1000mg/m2 on d1,8 with carboplatin AUC=5 on d1 intravenously, every 3 weeks, up to 4 cycles

Also known as: Gemzar

gemcitabine/carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stage IIIB (cytological confirmed with malignant pleural effusion or pericardial effusion) or histopathological or cytological confirmed stage IV NSCLC or relapsed after complete resection .
• EGFR exon19 deletions or exon 21 L858R mutation by the DNA direct PCR sequencing using fresh tumor sample or paraffin embed tumor sample.
• Measurable lesions as defined by RECIST criteria .
• 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.
• Patients with operation are allowed if the operation is 4 weeks before the first drug administration
• Men or women of at least 18 years of age.
• ECOG Performance status of 0 to 2.
• Estimated life expectancy of at least 12 weeks.
• Patient compliance and geographic proximity that allow adequate follow-up.
• 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.
• Informed consent from the patient.

You may not qualify if:

• 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)
• Wild type EGFR.
• Uncontrolled pericardial or pleural effusions prior to study entry.
• 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
• Brain metastasis (controlled brain metastasis and steroid free need is excluded).
• HIV infection
• Active infection, \>grade 2 in Common Terminology Criteria for Adverse Events(CTCAE) version 3.
• A history of operation or serious traumatic 3 weeks before the first drug administration
• 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 \[including Ta and Tis\]
• Mixed with small cell lung cancer
• Unable to swallow drugs.
• Malabsorption
• Pregnant or child breast feeding women
• 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.

Sponsors & Collaborators

• Tongji University: lead
• Sun Yat-sen University: collaborator
• Shanghai Chest Hospital: collaborator
• RenJi Hospital: collaborator
• Guangdong Provincial People's Hospital: collaborator
• Peking Union Medical College Hospital: collaborator

Study Sites (1)

Medical Department, Shanghai Pulmonary Hospital

Shanghai, 200433, China

Location

Related Publications (2)

• Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015 Sep;26(9):1877-1883. doi: 10.1093/annonc/mdv276. Epub 2015 Jul 3.

  PMID: 26141208 DERIVED

• Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011 Aug;12(8):735-42. doi: 10.1016/S1470-2045(11)70184-X. Epub 2011 Jul 23.

  PMID: 21783417 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride; Gemcitabine; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Study Officials

• Caicun Zhou, MD & PhD

  Tongji University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Shanghai Pulmonary Hospital

Study Record Dates

• First Submitted: April 1, 2009
• First Posted: April 2, 2009
• Study Start: August 1, 2008
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2012
• Last Updated: September 25, 2014

Record last verified: 2014-09

Locations

CN (1)