Afatinib Genomic Landscape

NCT02491775 | Terminated

• 1 other identifier: 201408008
• Study Type: observational
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose to conduct a pilot feasibility study of single agent afatinib in patients with previously untreated metastatic EGFR (epidermal growth factor receptor) mutant adenocarcinoma of the lung (NSCLC = non-small cell lung cancer) with the sole purpose of characterizing the genomic landscape before afatinib and at the time of disease progression.

Conditions

Carcinoma, Non-Small-Cell Lung; Non-Small Cell Lung Cancer; Non-small Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Genetic changes associated with disease progression following treatment with afatinib

  * The investigators will compare tumor sequencing prior to afatinib treatment to the time of disease progression to see if the genetic sequencing changed between pre-treatment and progression. * The investigators plan to conduct exome and transcriptome sequencing of tumor before therapy with afatinib and at the time of relapse. In addition, exome sequencing of peripheral blood DNA will be done (for germline). Given the complexities of genomic analyses of paired samples in the face of limited data, the investigators will not be able to do any formal power calculations in this feasibility study. * Disease progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

  Estimated to be 1 year

Secondary Outcomes (2)

• Types of mutations in signaling kinases associated with therapeutic response

  Estimated to be 1 year

• Allelic ratio of wild type to mutant EGFR (roughly corrected for intrinsic differences in tumor cellularity) with duration of response

  Estimated to be 1 year

Eligibility Criteria

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

Study Population

Participants will be selected from the Washington University School of Medicine and Barnes-Jewish healthcare system who previously consented to study HRPO (Human Research Protection Office)# 201305031 ("Tissue and Blood Acquisition for Genomic Analysis and Collection of Health Information from Patients with Thoracic Malignancies, Suspected Thoracic Malignancies, or Mesothelioma").

You may not qualify if:

• Diagnosis of metastatic stage IIIB/IV lung adenocarcinoma
• Presence of known sensitizing mutations in EGFR TK domain (exon 19 deletion and L858R)
• Absence of known resistant mutations in the EGFR TK domain (T790M)
• Consented to HRPO # 201305031 ("Tissue and Blood Acquisition for Genomic Analysis and Collection of Health Information from Patients with Thoracic Malignancies, Suspected Thoracic Malignancies, or Mesothelioma")
• No prior treatment for this malignancy
• No prior localized therapy to the biopsy site
• Planned treatment with standard of care afatinib at 40 mg QD (daily)
• Not pregnant or breastfeeding
• At least 18 years of age

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

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

Study Officials

• Ramaswamy Govindan, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2015
• First Posted: July 8, 2015
• Study Start: June 11, 2015
• Primary Completion: February 28, 2018
• Study Completion: February 28, 2018
• Last Updated: March 5, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)