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A Window of Opportunity Trial of Afatinib In Early Stage Non-Small Cell Lung Cancer (NSCLC)

Primary Purpose

Lung Cancer

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

BIBW 2992 (Afatinib)

About this trial

This is an interventional treatment trial for Lung Cancer

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histologically confirmed NSCLC, who are deemed to be surgical candidates by standard criteria. Patients with all histologies will be allowed to enroll.

Patients with Stage IA to IIIA disease

ECOG Performance Status 0-1
Measurable disease by RECIST 1.1 criteria
Mediastinoscopy and/or Endoscopic Bronchial Ultrasound (EBUS) and/or Endoscopic Ultrasound (EUS) for complete surgical staging when clinically indicated
Total bilirubin ≤1.5 mg/dl, SGOT (AST) and SGPT (ALT)≥ 3 x ULN
Serum creatinine ≤ 1.5 mg/dl
Serious, active infections must be controlled. Patients may be enrolled while still on antibiotics as long as clinical signs of active infection have resolved.
A signed informed consent document (ICD)
Patients 18 years or older
Able and willing to take oral medications

Exclusion Criteria:

Known preexisting lung disease.
History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to randomization.
Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g. Crohn's disease, malabsorption or CTC grade ≥2 diarrhea of any etiology.
Baseline (<1 month before treatment) cardiac left ventricular function with resting ejection fraction of less than 50% measured by multigated blood pool imaging of the heart (MUGA scan) or echocardiogram
Patients may not be receiving any other investigational agents.
History of allergic reactions to anilinoquinazolins like gefitinib, erlotinib or BIBW 2992
Uncontrolled intercurrent illness that would preclude a patient from undergoing surgery
Psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant (positive pregnancy test) or lactating
Inability to comply with study and/or follow-up procedures
Patients who are not surgical candidates or refuse surgery

Sites / Locations

Medical University of South Carolina

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single Arm Study

Arm Description

Single arm trial where all patients will be treated with afatinib until the day of surgery and for a minimum of two weeks. Patients will receive treatment with afatinib 40mg orally daily.

Outcomes

Primary Outcome Measures

Feasibility

The primary endpoint will demonstrate feasibility of neoadjuvant treatment of BIBW 2992 in patients with early stage (IA to IIIA) NSCLC awaiting surgical resection. Feasibility will be assessed based on the ability to complete the treatment for each patient. For our feasibility endpoint we will declare the treatment "completed" if a patient completes at least 14 days of treatment, had a thoracotomy for the planned surgical resection, and 30 days of post operative care.

Secondary Outcome Measures

Safety and Efficacy

The secondary objective is to determine whether pre-operative BIBW 2992 treatment affects metabolic tumor labeling, as measured by PET-CT scanning. We will measure the absolute and the percentage change in SUV from baseline to follow-up.

Full Information

NCT ID

NCT01480141

First Posted

November 23, 2011

Last Updated

March 25, 2013

Sponsor

Medical University of South Carolina

Collaborators

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT01480141

Brief Title

A Window of Opportunity Trial of Afatinib In Early Stage Non-Small Cell Lung Cancer (NSCLC)

Official Title

A Therapeutic Trial of Afatinib in the Neoadjuvant Setting. Molecular Effects of Afatinib: A Window of Opportunity Trial In Early Stage NSCLC

Study Type

Interventional

2. Study Status

Record Verification Date

September 2012

Overall Recruitment Status

Withdrawn

Why Stopped

PI left MUSC, no patient enrollments

Study Start Date

January 2012 (undefined)

Primary Completion Date

August 2012 (Actual)

Study Completion Date

August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Medical University of South Carolina

Collaborators

Boehringer Ingelheim

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study is for patients that have Non-Small Cell Lung Cancer (NSCLC) and he or she will have surgery to remove the tumor. The main purpose of this study is to study how safe and suitable treatment with Afatinib is in participants before surgery to remove the tumor. Another goal of the study is to see if treatment with Afatinib affects the growth and activity of the tumor. Afatinib has not been approved for use by the FDA (Food and Drug Administration) and is experimental. In some persons, the growth of cancer cells is thought to be stimulated by Epidermal Growth Factor (EGF). This is a protein found in the body which binds to the cell wall to sites called receptors and stimulates cell growth. Some cells have too many receptors and uncontrolled growth and because of this, develop into a cancer tumor. There are several other cancer drugs that bind to these receptors to slow or stop cancer growth such as Gefitinib and erlotinib which are FDA approved and used for the treatment of NSCLC. The drug Afatinib has been shown to inhibit mutated EGF receptors in clinical trials and may be a candidate for the treatment of NSCLC and a variety of early stage cancers. Participants in this study will take Afatinib by mouth, in pill form, for at least 14 days before having their scheduled surgery to remove their cancer tumor. Participants will be observed for side effects and followed for 30 days after surgery to assess the results after surgery.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lung Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Single Arm Study

Arm Type

Experimental

Arm Description

Single arm trial where all patients will be treated with afatinib until the day of surgery and for a minimum of two weeks. Patients will receive treatment with afatinib 40mg orally daily.

Intervention Type

Drug

Intervention Name(s)

BIBW 2992 (Afatinib)

Intervention Description

Patients will receive treatment with afatinib 40mg orally daily for a minimum of 2 weeks

Primary Outcome Measure Information:

Title

Feasibility

Description

Time Frame

30 days post operative care

Secondary Outcome Measure Information:

Title

Safety and Efficacy

Description

Time Frame

30 post operative care

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically confirmed NSCLC, who are deemed to be surgical candidates by standard criteria. Patients with all histologies will be allowed to enroll. Patients with Stage IA to IIIA disease ECOG Performance Status 0-1 Measurable disease by RECIST 1.1 criteria Mediastinoscopy and/or Endoscopic Bronchial Ultrasound (EBUS) and/or Endoscopic Ultrasound (EUS) for complete surgical staging when clinically indicated Total bilirubin ≤1.5 mg/dl, SGOT (AST) and SGPT (ALT)≥ 3 x ULN Serum creatinine ≤ 1.5 mg/dl Serious, active infections must be controlled. Patients may be enrolled while still on antibiotics as long as clinical signs of active infection have resolved. A signed informed consent document (ICD) Patients 18 years or older Able and willing to take oral medications Exclusion Criteria: Known preexisting lung disease. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to randomization. Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g. Crohn's disease, malabsorption or CTC grade ≥2 diarrhea of any etiology. Baseline (<1 month before treatment) cardiac left ventricular function with resting ejection fraction of less than 50% measured by multigated blood pool imaging of the heart (MUGA scan) or echocardiogram Patients may not be receiving any other investigational agents. History of allergic reactions to anilinoquinazolins like gefitinib, erlotinib or BIBW 2992 Uncontrolled intercurrent illness that would preclude a patient from undergoing surgery Psychiatric illness/social situations that would limit compliance with study requirements. Pregnant (positive pregnancy test) or lactating Inability to comply with study and/or follow-up procedures Patients who are not surgical candidates or refuse surgery

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

George Simon, MD

Organizational Affiliation

Medical University of South Carolina Hollings Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Medical University of South Carolina

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

12. IPD Sharing Statement

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A Window of Opportunity Trial of Afatinib In Early Stage Non-Small Cell Lung Cancer (NSCLC)

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