A Study on the Correlation Between Tarceva (Erlotinib) - Induced Rash and Efficacy in EGFR Mutated Participants With Advanced Non-Small Cell Lung Cancer Receiving First-Line Therapy

A Multi-Center Study Investigating the Correlation Between TARCEVA ®-Induced Rash and Efficacy Among EGFR-mutated NSCLC Patients Receiving First-line Therapy

This open-label, single arm study will assess the correlation between Tarceva (erlotinib)-induced rash and efficacy in participants with inoperable, locally advanced, recurrent or metastatic non-small cell lung cancer (NSCLC) receiving first-line therapy for advanced disease. Participants will receive Tarceva at a dose of 150 mg daily orally, with dose adjustments according to protocol depending on toxicity. Anticipated time on study treatment is until disease progression, unacceptable toxicity, or withdrawal due to any reason.

Study Overview

• Status: Completed
• Conditions: Non-Squamous Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: erlotinib [Tarceva]

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Afula, Israel, 18101
    • Haemek Hospital; Oncology
  • Ashkelon, Israel, 78278
    • Barzilai; Oncology
  • Beer Sheva, Israel, 8410101
    • Soroka Medical Center; Oncology Dept
  • Haifa, Israel, 3525408
    • Rambam Medical Center; Oncology
  • Haifa, Israel, 34362
    • Carmel Hospital; Oncology Unit
  • Holon, Israel, 58100
    • Wolfson Hospital; Oncology
  • Jerusalem, Israel, 91031
    • Shaare Zedek Medical Center; Oncology Dept
  • Jerusalem, Israel, 9112001
    • Hadassah Ein Karem Hospital; Oncology Dept
  • Kfar-Saba, Israel, 4428164
    • Meir Medical Center; Oncology
  • Nahariya, Israel, 22100
    • Nahariya Hospital; Oncology
  • Ramat Gan, Israel, 5262100
    • Chaim Sheba Medical Center; Oncology Dept
  • Rehovot, Israel, 7610001
    • Kaplan Medical Center; Oncology Inst.
  • Sefad, Israel, 13100
    • Ziv Medical Center; Oncology Department
  • Tel Aviv, Israel, 64239-06
    • Sourasky / Ichilov Hospital; Oncology Department
  • Tiberias, Israel, 15208
    • Poria Hospital; Oncology
  • Zerifin, Israel, 6093000
    • Assaf Harofeh; Oncology

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:

• Adult participants, >/= 18 years of age
• Inoperable, locally advanced, recurrent or metastatic (Stage IIIB or IV) non-small cell lung cancer (NSCLC)
• Presence of epidermal growth factor receptor (EGFR) mutations
• Previously untreated with any systemic anti-neoplastic therapy for advanced disease
• Last dose of a prior systemic anti-neoplastic therapy for early-stage disease >/= 4 weeks before study start, and patient recovered from acute toxicities of any previous therapy
• A life expectancy of at least 12 weeks
• Able to comply with the study and its follow-up procedures
• Female participants had to be postmenopausal (24 months of amenorrhea), surgically sterile or agree to use a physical method of contraception. Male participants had to be surgically sterile or agree to use a barrier method of contraception. Women with an intact uterus (unless amenorrhoeic for the last 24 months) had to have a negative pregnancy test (urine or serum) within 3 days prior to erlotinib treatment initiation in the study. Male and female participants had to use effective contraception during the study and for a period of 90 days following the last administration of erlotinib. Acceptable methods of contraception included an established hormonal therapy or intrauterine device for females, and the use of a barrier contraceptive (i.e. diaphragm or condoms)

Exclusion Criteria:

• Pregnant or breast feeding women
• Granulocyte count <1.5 x 109/L and platelet count <100*10^9/L
• Serum bilirubin >1.5 upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2 * ULN (or >5 * ULN if clearly attributable to liver metastasis)
• Serum creatinine >1.5 ULN or creatinine clearance <60 mL/min
• Known allergy or other adverse reaction to study drug or any other related compound
• Any significant unstable systemic disease (including active infection, grade 4 hypertension, unstable angina, congestive heart failure, hepatic, renal or metabolic disease)
• Prior systemic anti-neoplastic therapy with HER1/EGFR inhibitors (as small molecule or monoclonal antibody therapy)
• Newly diagnosed or not yet definitively treated (i.e. stable disease >/= 2 months) CNS metastases or spinal cord compression
• Any significant ophthalmological abnormality, especially those likely to increase the risk of corneal epithelial lesions (the use of contact lenses is not recommended during the study)
• Participants who could not take oral medication, who required intravenous alimentation, had had prior surgical procedures affecting absorption, or had active peptic ulcer disease
• Active cancer other than NSCLC, except for basal cell or squamous cell carcinomas of the skin that have been excised and cured

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm	Drug: erlotinib [Tarceva]; 150 mg orally daily, with dose-reductions to 100 mg or 50 mg orally daily according to protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) According to Grade of Rash	PFS was defined as the time from start of treatment to the date of the first documented progression according to revised Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 or the date of death for any reason in the absence of progressive disease (PD). Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.	Day 1 of treatment period until disease progression or death (approximately up to 67 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Erlotinib Dose Reductions Due to Rash Grade 3-4		Day 1 of treatment period until disease progression or death (approximately up to 67 months)
Progression-Free Survival (PFS) in Participants With Erlotinib Dose Reductions Due to Rash Grade 3-4	PFS was defined as the time from start of treatment to the date of the first documented progression according to revised Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 or the date of death for any reason in the absence of progressive disease (PD). Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.	Day 1 of treatment period until disease progression or death (approximately up to 67 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: Clalit Health Services

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2011
• Primary Completion (Actual): December 20, 2016
• Study Completion (Actual): December 20, 2016

Study Registration Dates

• First Submitted: August 2, 2010
• First Submitted That Met QC Criteria: August 2, 2010
• First Posted (Estimate): August 3, 2010

Study Record Updates

• Last Update Posted (Actual): September 17, 2018
• Last Update Submitted That Met QC Criteria: September 14, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• 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; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: ML25200