Erlotinib Versus Pemetrexed as Second-Line Therapy in Treating Patients With Advanced Lung Adenocarcinoma

• ClinicalTrials.gov Identifier: NCT01565538
• Recruitment Status: Completed
• First Posted: March 28, 2012
• Results First Posted: September 15, 2014
• Last Update Posted: September 15, 2014
• Sponsor: Si-Yu Wang
• Information provided by (Responsible Party): Si-Yu Wang, Sun Yat-sen University

Study Description

Brief Summary:

Both pemetrexed and erlotinib are second-line treatment options for patients with advanced non-small cell lung cancer. It is controversial that whether it is necessary to detect epidermal growth factor receptor (EGFR) mutation status for the EGFR-targeted therapy after the failure of standard chemotherapy. The role of EGFR gene copy number as a predictive marker remains controversial. Therefore, we investigate the efficacy of erlotinib and pemetrexed as second-line therapy in treating in patients with EGFR wild-type and EGFR FISH-positive advanced lung adenocarcinoma.

Condition or disease	Intervention/treatment	Phase
Lung Cancer	Drug: Erlotinib; Drug: Pemetrexed	Phase 2

Detailed Description:

Standard first-line treatment for advanced-stage non-small cell lung cancer (NSCLC) usually consists of platinum-based doublet chemotherapy, but progression ultimately occurs for most patients. Second-line treatment options available to patients who suffer failure of first-line treatment include further chemotherapy (docetaxel and pemetrexed) or targeted therapy. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) show great efficacy in patients with advanced NSCLC with EGFR mutation. High EGFR gene copy number was associated with great sensitivity and prolonged progression-free survival of NSCLC from EGFR-TKIs. This phase II study was designed to assess the efficacy and safety of erlotinib compared with pemetrexed as second-line treatment for EGFR wild-type and EGFR FISH-positive lung adenocarcinoma.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 123 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Trial of Erlotinib Versus Pemetrexed as Second-Line Therapy in Treating Patients With Advanced EGFR Wild-Type and EGFR FISH-Positive Lung Adenocarcinoma
• Study Start Date: December 2008
• Actual Primary Completion Date: May 2012
• Actual Study Completion Date: May 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Erlotinib; Erlotinib at the dose of 150 mg orally once a day continually until progression.	Drug: Erlotinib; 150 mg Given orally; Other Name: Tarceva
Experimental: Pemetrexed; Pemetrexed at the dose of 500mg/m2 IV infusion every 3 weeks until progression.	Drug: Pemetrexed; 500mg/m2 Given IV; Other Name: ALIMTA

Outcome Measures

Primary Outcome Measures :

1. Progression-Free Survival [ Time Frame: From the date of randomization to the date of tumour progression or death from any cause, assessed until at least 12 months after randomization. ]
   Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures :

1. Best Tumor Response [ Time Frame: From the date of randomization, assessed every 6 weeks, until at least 12 months after randomization. ]
   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
2. Overall Survival [ Time Frame: From date of randomization until the date of death from any cause, assessed until at least 12 months after randomization. ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed Lung adenocarcinoma
• Wld-type EGFR
• Stage IIIB/IV
• Failure to prior chemotherapy
• Life expectancy of more than 3 months
• Tissue sample desired for genomic study
• Age ≥ 18 years
• Performance status (WHO) < 3
• Adequate bone marrow function (absolute neutrophil count > 1000/mm^3, platelet count > 100000/mm^3, hemoglobin > 9gr/mm^3)
• Adequate liver (bilirubin < 1.5 times upper limit of normal and SGOT/SGPT < 2 times upper limit of normal) and renal function (creatinine < 2mg/dl)
• Presence of two-dimensional measurable disease. The measurable disease should not have been irradiated
• Informed consent

Exclusion Criteria:

• Have previously received pemetrexed or TKIs
• Other concurrent uncontrolled illness

Contacts and Locations

Locations

China, Guangdong

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China, 510060

Sponsors and Collaborators

Si-Yu Wang

Investigators

• Principal Investigator: Si-Yu Wang, Doctor; Sun Yat-sen University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Li N, Ou W, Yang H, Liu QW, Zhang SL, Wang BX, Wang SY. A randomized phase 2 trial of erlotinib versus pemetrexed as second-line therapy in the treatment of patients with advanced EGFR wild-type and EGFR FISH-positive lung adenocarcinoma. Cancer. 2014 May 1;120(9):1379-86. doi: 10.1002/cncr.28591. Epub 2014 Jan 30.

• Responsible Party: Si-Yu Wang, Professor, Sun Yat-sen University
• ClinicalTrials.gov Identifier: NCT01565538
• Other Study ID Numbers: wsy001
• First Posted: March 28, 2012
• Results First Posted: September 15, 2014
• Last Update Posted: September 15, 2014
• Last Verified: September 2014

Keywords provided by Si-Yu Wang, Sun Yat-sen University:

Cancer; Non-small-cell lung cancer; Adenocarcinoma; EGFR gene mutation; Chemotherapy; Pemetrexed; Erlotinib

Additional relevant MeSH terms:

Adenocarcinoma; Adenocarcinoma of Lung; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Erlotinib Hydrochloride; Pemetrexed; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors