Randomized Comparative Study of Erlotinib and Pemetrexed in the Maintenance Treatment of Advanced Lung Cancer Patients.

Randomized Multicenter Study to Compare the Effectiveness and Safety of Erlotinib and Pemetrexed as Maintenance Therapy of Advanced Non-Squamous Non-Small Cell Lung Cancer

The purpose of this multicenter randomized study is to compare the effectiveness and safety of erlotinib and pemetrexed in the maintenance treatment of patients with advanced non-squamous non-small cell lung cancer (NSCLC)

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Pemetrexed; Drug: Erlotinib

Detailed Description

A randomized multi-center prospective study to compare the 12-month effectiveness (survival) and safety of erlotinib and pemetrexed as maintenance treatment in two groups of patients with locally advanced or metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) other than predominantly squamous cell histology, whose disease has not progressed immediately following platinum-based chemotherapy for 4 cycles administered per routine daily practice in each study center

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 4

Contacts and Locations

Study Locations

• Jordan
  • Amman, Jordan, 11118
    • King Hussein Cancer Center (KHCC)
• Lebanon
  • Beirut, Lebanon, 1107 2020
    • American University of Beirut Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years
• Signed written informed consent
• Histologically or cytological diagnosed stage IIIB/IV non-squamous histology NSCLC
• Received platinum based doublet chemotherapy for 4 cycles as first line therapy before this study
• Patients upon enrolment has at least stable disease following the platinum doublet; with documented (confirmed or unconfirmed) radiographic evidence of a tumor response of complete response (CR), partial response (PR), or stable disease (SD) according to RECIST version 1.1 criteria
• Estimated Life expectancy ≥ 3 months
• Eastern cooperative oncology group performance status (ECOG PS) 0-2
• Adequate organ function

Exclusion Criteria:

• Age ˂18 years
• Predominantly squamous cell and/or mixed small cell, non-small cell histology
• Current treatment on another therapeutic clinical study or within the last 30 days of entering the study
• Spinal cord compression unless treated with the patient attaining good pain control and stable or recovered neurologic function, carcinomatous meningitis, or leptomeningeal disease
• Any of the following within the 3 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack
• Ongoing cardiac dysrhythmias of national cancer institute-common terminology criteria for adverse events (NCI CTCAE) Grade >2, uncontrolled atrial fibrillation of any grade, or corrected QT interval (QTc) >470 msec
• Pregnancy or breastfeeding
• Prior malignancy (other than current NSCLC): patients will not be eligible if they have evidence of active malignancy (other than non-melanoma skin cancer or localized cervical cancer, or localized and presumed cured prostate cancer) within the last 3 years
• Other severe acute or chronic medical or psychiatric conditions, or laboratory abnormalities that would impose, in the judgment of the investigator and/or sponsor, excessive risk associated with study participation or study drug administration, and which would, therefore, make the patient inappropriate to enter this study
• Uncontrolled third-space fluid collections
• Progressive brain metastases
• Hypersensitivity to the study drugs
• Inability to take corticosteroid drugs, folic acid, or vitamin B12
• Patients with epidermal growth factor receptor (EGFR) positive, anaplastic lymphoma kinase (ALK) positive (documented using fluorescence in situ hybridization (FISH) and/or immunohistochemistry (IHC)), or unknown EGFR and ALK test results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Pemetrexed Arm; Vials containing powder for concentrate for solution for infusion equivalent to 500 mg of pemetrexed (as disodium)	Drug: Pemetrexed; Vials containing powder for concentrate for solution for infusion equivalent to 500 mg of pemetrexed (as disodium) administered as 500mg/m2 IV over 10 minutes on the first day of each 21-day cycle, until disease progression or unacceptable toxic effects; Other Names: Pemitra®
Other: Erlotinib Arm; Film coated tablets containing 150 mg erlotinib (as erlotinib hydrochloride)	Drug: Erlotinib; Film coated tablets containing 150 mg erlotinib (as erlotinib hydrochloride) administered once daily until disease progression or unacceptable toxic effects; Other Names: Mirata®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) in eligible patients randomized to erlotinib or pemetrexed treatment arms	Progression Free Survival is defined as the time from date of randomization to the date of tumor progression or death from any cause, assessed until at least 12 months after randomization. Progression is defined using response evaluation criteria in solid tumors (RECIST version 1.1)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Overall Survival (OS) Time between eligible patients randomized to erlotinib or pemetrexed treatment of therapy	Overall survival time is defined as the time from date of randomization until the date of death from any cause, assessed until at least 12 months after randomization	12 months
Overall response rate and duration between eligible patients randomized to erlotinib or pemetrexed treatment arms	Overall response defined using RECIST version 1.1 and the duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or progressive disease (PD) is objectively documented (taking as reference for PD the smallest measurements recorded since the treatment started) or until at least 12 months after randomization as assessed every 6 weeks	12 months
Incidence of adverse events (AEs) and serious adverse events (SAEs) to erlotinib and pemetrexed	Incidence rates, severity, relationship of adverse events (AEs) and serious AE (SAE) to treatment drugs, number of AEs leading to permanent treatment discontinuation and clinically relevant changes in laboratory tests will be recorded, estimated and presented	12 months

Collaborators and Investigators

• Sponsor: Hikma Pharmaceuticals LLC

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2018
• Primary Completion (Actual): November 14, 2018
• Study Completion (Actual): November 14, 2018

Study Registration Dates

• First Submitted: February 26, 2018
• First Submitted That Met QC Criteria: March 8, 2018
• First Posted (Actual): March 9, 2018

Study Record Updates

• Last Update Posted (Actual): March 5, 2020
• Last Update Submitted That Met QC Criteria: March 3, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: NSCLC; Tyrosine kinase inhibitor; Maintenance Therapy; Non-squamous; Randomized Study; Generic Erlotinib; Generic Pemetrexed; Antifolate antineoplastic agents
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Folic Acid Antagonists; Erlotinib Hydrochloride; Pemetrexed
• Other Study ID Numbers: MRT-JOR-LEB-KSA-2016-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No