Erlotinib Therapy and Subsequent Development of Mechanisms of Secondary Resistance in Patients With NSCLC

NCT00997334 | Completed Phase 2 Results DMC

• 2 other identifiers: 09-210NE_OSI4590s
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

Erlotinib is a drug which targets non small cell lung cancer with a genetic change (mutation) in the epidermal growth factor receptor (EGFR). This drug has been used in other cancer research studies and information from those studies suggests that Erlotinib can control the growth of these cancer cells.

Conditions

Non-small Cell Lung Cancer

Keywords

erlotinib; EGFR mutation; NSCLC

Outcome Measures

Primary Outcomes (1)

• Resistance Mechanism

  Participants were classified into 4 potential resistant mechanism groups (4 genetic/ 1 histologic) based on evaluation of rebiopsy tissue: EGFR mutations (T790M mutation, exon 20 insertion), KRAS mutations, MET amplification or small-cell lung cancer (SCLC) transform using established methods.

  Participants were evaluated for incidence of genetic mechanisms of secondary resistance at time of disease progression at which point participants stopped treatment. Progression follow up was up to 3 years in this study cohort.

Secondary Outcomes (1)

• Progression-Free Survival

  Disease was evaluated radiologically every 8 weeks on treatment (cycle duration=4 weeks). Participants were treated until evidence of disease progression or unacceptable toxicity. Progression follow-up was up to 3 years in this study cohort.

Study Arms (1)

Erlotinib

EXPERIMENTAL

Erlotinib was given at a dose of 150mg orally once per day for 28 days (+/- 3 days); Patients are treated until disease progression or until unaccepted drug toxicity.

Drug: Erlotinib

Interventions

Erlotinib DRUG

Also known as: Tarceva

Erlotinib

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed non-small cell lung cancer, stage IV or IIIB with a malignant pleural or pericardial effusion. Patients with stage I or II non-small cell lung cancer who have undergone surgical resection but who subsequently relapse with metastatic disease or a malignant pleural effusion are also eligible.
• Documentation of a sensitizing mutation of the epidermal growth factor receptor. In addition, there must be a sufficient tissue for analysis of KRAS (the oncogene from the Kirsten rat sarcoma virus) mutations and MET amplification.
• At least one measurable or evaluable site of disease as defined by revised RECIST (version 1.1) criteria.
• years of age or older
• No more than one prior systemic therapy regimen for advanced non-small cell lung cancer. Chemotherapy delivered as part of concurrent chemoradiation will also count as a prior systemic therapy regimen. Adjuvant therapy for resected NSCLC will not count towards this total as long as it was completed at least 6 months prior to enrollment and did not include therapy with an EGFR-targeted agent. Adjuvant therapy completed less than 6 months prior to the time of screening will count as a prior regimen.
• or more weeks since prior major surgery
• or more weeks since prior radiation
• ECOG performance status 0-1
• Life expectancy \> 8 weeks
• Adequate hematologic, renal, and hepatic function
• Willingness to undergo repeat tumor biopsy at the time of disease progression.

You may not qualify if:

• Untreated and/or uncontrolled central nervous system metastases. Patients with prior brain metastases must have had definitive treatment (radiation or surgery) and must be clinically stable off steroids for at least 1 week prior to enrollment.
• More than one prior systemic chemotherapy for advanced non-small cell lung cancer. , Chemotherapy delivered as part of concurrent chemoradiation will also count as a prior systemic therapy regimen. Adjuvant therapy for resected NSCLC willnot count towards this total as long as it was completed at least 6 months prior to enrollment and did not include therapy with an EGFR-targeted agent. Adjuvant therapy completed less than 6 months prior to the time of screening will count as a prior regimen.
• Prior exposure to erlotinib or other treatments targeting the HER family axis.
• Active malignancies within the past 3 years, except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
• Any process that compromises the ability to swallow and/or absorb oral medication.
• Incomplete healing from previous surgery
• A history of any of the following autoimmune skin disorders: Sjogren's syndrome, scleroderma, dermatomyositis, and systemic lupus erythematosus.
• Significant medical history or unstable medical conditions.
• Concurrent use of warfarin. Patients must be off warfarin for at least one week prior to initiation of erlotinib. Other non-warfarin anticoagulants are permitted.
• Patients who require ongoing concomitant use of one of the strong inhibitors/inducers of CYP3A4.
• Pregnant or breastfeeding. Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation.

Sponsors & Collaborators

• David M. Jackman, MD: lead
• Beth Israel Deaconess Medical Center: collaborator
• Brigham and Women's Hospital: collaborator
• Genentech, Inc.: collaborator

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Redig AJ, Costa DB, Taibi M, Boucher D, Johnson BE, Janne PA, Jackman DM. Prospective Study of Repeated Biopsy Feasibility and Acquired Resistance at Disease Progression in Patients With Advanced EGFR Mutant Lung Cancer Treated With Erlotinib in a Phase 2 Trial. JAMA Oncol. 2016 Sep 1;2(9):1240-2. doi: 10.1001/jamaoncol.2016.1304. No abstract available.

  PMID: 27387964 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: David M. Jackman, MD
• Organization: Dana-Farber Cancer Institute

David_Jackman@dfci.harvard.edu

617.632.3468

Study Officials

• David Jackman, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 16, 2009
• First Posted: October 19, 2009
• Study Start: February 1, 2010
• Primary Completion: May 1, 2015
• Study Completion: January 1, 2017
• Last Updated: February 23, 2018
• Results First Posted: April 11, 2017

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)