A Study to Assess Biomarkers Impact on Participants Response to Erlotinib Treatment for First-line Non-Small Cell Lung Cancer With Endothelial Growth Factor Receptor (EGFR) Activating Mutations (BIOTEC)

• ClinicalTrials.gov Identifier: NCT01153984
• Recruitment Status: Completed
• First Posted: June 30, 2010
• Results First Posted: April 13, 2017
• Last Update Posted: April 13, 2017
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

This open-label, single-arm, multi-center study will evaluate the progression-free survival in participants with histologically documented, advanced and/or metastatic chemotherapy naive, non-small cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) positive mutations and receiving erlotinib treatment. The anticipated time on study treatment is until disease progression, unacceptable toxicity, withdrawal due to any reason or death.

Condition or disease	Intervention/treatment	Phase
Carcinoma，Non-Small-Cell Lung	Drug: Erlotinib	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Biomarkers Impact on the Response to Treatment With Erlotinib in First Line Non-small Cell Lung Cancer With EGFR Activating Mutations - BIOTEC
• Study Start Date: June 2011
• Actual Primary Completion Date: July 2015
• Actual Study Completion Date: July 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Erlotinib; Participants will receive 150 milligrams (mg) erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death.	Drug: Erlotinib; Erlotinib 150 mg oral doses will be administered daily.; Other Name: Tarceva

Outcome Measures

Primary Outcome Measures :

1. Progression-Free Survival (PFS), as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: Baseline up to approximately 4 years ]
   PFS was the time from inclusion in the study to the date of first documented PD or death from any cause, whichever occurred first. Participants without event were censored at the date of the last tumor assessment where non-progression was documented. If a participant received a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. Analysis was performed using Kaplan-Meier method. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.

Secondary Outcome Measures :

1. Time to Disease Progression, as Assessed by Investigator Using RECIST v1.1 [ Time Frame: Baseline up to approximately 4 years ]
   Time to disease progression was defined as the time from baseline evaluation to the first date PD was recorded. Participants without progression were censored at the date of last tumor assessment where non-progression was documented. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.
2. Percentage of Participants With Complete Response (CR) And Partial Response (PR) as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: Baseline up to approximately 4 years ]
   CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to baseline.
3. Percentage of Participants Who Were Alive One Year After Study Treatment Initiation [ Time Frame: Year 1 ]
4. Percentage of Participants by Localization of PD, as Assessed by Investigator Using RECIST v1.1 [ Time Frame: Baseline up to approximately 4 years ]
   PD was assessed using RECIST v1.1. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. Percentage of participants by localization of PD were reported. Localization included: Left lung inferior lobe; Para-aortic; Left lung upper lobe; Right lung inferior lobe; and Infracranial.
5. Number of EGFR Positive Participants Classified Based on Smoking Status [ Time Frame: Day 1 ]
   Participants were asked: "Have you smoked at least 100 cigarettes in your entire life?" and "Do you now smoke cigarettes every day, some days, or not at all?" Responses were grouped into three categories: Current Smoker, Former Smoker, and Non-Smoker. Participants who reported smoking at least 100 cigarettes in their lifetime and who, at the time of survey, smoked either every day or some days were defined as 'Current smoker'. Participants who reported smoking at least 100 cigarettes in their lifetime and who, at the time of the survey, did not smoke at all were defined as 'Former smoker'. Participants who reported never having smoked 100 cigarettes were defined as 'Non-smoker'.
6. Number of EGFR Positive Participants Classified Based on Type of EGFR Mutations [ Time Frame: Day 1 ]
   Participants with NSCLC have tumor associated with EGFR mutations. These mutations occur within EGFR Exons 18-21, which encodes a portion of the EGFR kinase domain.
7. Percentage of Similar EGFR Mutations Between Matched Plasma and Tumor Tissue Samples [ Time Frame: Baseline up to approximately 4 years ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Histological documented adenocarcinoma, locally advanced - Stage IIIB, metastatic - Stage IV or recurrent non-squamous NSCLC
• Activated EGFR mutation positive status (Exons 19 and 21) for treatment phase
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy greater than or equal to (≥) 12 weeks
• Evidence of disease with at least one measurable disease evaluation on Response Evaluation Criteria in Solid Tumors (RECIST)
• Adequate hematological , liver and renal function

Exclusion Criteria:

• Known hypersensitivity to erlotinib or any of its excipients
• Squamous non-small cell or small cell tumors or absence of histological report
• Neoadjuvant/adjuvant chemotherapy within 6 months prior to enrollment
• Prior exposure to inhibitors of EGFR
• Prior chemotherapy or treatment with another systemic anti-cancer agent for the treatment of the participant's current stage of disease
• Any significant ophthalmologic abnormality, especially severe dry eye syndrome, keratoconjunctivitis sicca, Sjögren syndrome, severe exposure keratitis or any other disorder likely to increase the risk of corneal epithelial lesions
• Radical radiotherapy with curative intent within 28 days prior to enrollment
• Any active non-controlled systemic disease

Contacts and Locations

Locations

Romania

County Hospital Alba; Oncology

Alba Iulia, Romania, 510073

Institute Of Oncology Bucharest; Medical Oncology

Bucharest, Romania, 022338

Spitalul de Boli Cronice Sf. Luca

Bucharest, Romania, 04195

Emergency University Bucharest Hospital; Oncology Department

Bucharest, Romania, 050098

Institut of Oncology Al. Trestioreanu Bucharest; Oncology

Bucuresti, Romania, 022328

Oncology Inst. Cluj-Napoca; Cancer Dept

Cluj-Napoca, Romania, 400015

Uni Hospital St. Spiridon; Clinica Oncologie-Radiotherapie

Iasi, Romania, 6600

S.C. Life Search S.R.L; Medical Oncology Clinic

Timisoara, Romania, 300167

ONCOMED - Medical Centre

Timisoara, Romania, 300239

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01153984
• Other Study ID Numbers: ML22606; 2009-017063-42
• First Posted: June 30, 2010
• Results First Posted: April 13, 2017
• Last Update Posted: April 13, 2017
• Last Verified: February 2017

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Erlotinib Hydrochloride; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action