EVENT: Erlotinib Hydrochloride Before Surgery in Treating Patients With Stage III Non-Small Cell Lung Cancer

• Sponsor: Albert Einstein College of Medicine (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01857271
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 3
• Locations: 3
• Arm: 1
• Duration (Months): 46
• Patient Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies how well erlotinib hydrochloride works before surgery in treating patients with stage III non-small cell lung cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib hydrochloride before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Condition or Disease	Intervention/Treatment	Phase
Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer	Drug: Erlotinib Hydrochloride; Procedure: Therapeutic Conventional Surgery; Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To estimate the rate of mediastinal nodal clearance and complete pathological response after neoadjuvant erlotinib (erlotinib hydrochloride) in patients with epidermal growth factor receptor (EGFR) mutated stage III non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

1. To determine the progression free survival in patient population of EGFR mutated stage III NSCLC patients who are treated with neoadjuvant erlotinib therapy.

2. To determine the overall survival. III. To estimate the overall response rate from neoadjuvant erlotinib. IV. To estimate the surgical resection rate. V. To evaluate the safety of neoadjuvant erlotinib.

TERTIARY OBJECTIVES:

1. To determine several molecular and cellular biomarkers in the tumors, the skin and the serum that are predictive of the efficacy of neoadjuvant erlotinib.

OUTLINE:

Patients receive erlotinib hydrochloride orally (PO) once daily (QD) for 2 months and then undergo thoracotomy.

After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, and then every 6 months for 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: EValuation of Erlotinib as a Neoadjuvant Therapy in Stage III NSCLC Patients With EGFR Mutations (EVENT Trial)
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Aug 31, 2017
• Actual Study Completion Date: Aug 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (erlotinib hydrochloride and thoracotomy) Patients receive erlotinib hydrochloride PO QD for 2 months and then undergo thoracotomy.	Drug: Erlotinib Hydrochloride; Given PO; Other Names: Cp-358,774 ; Procedure: Therapeutic Conventional Surgery; Undergo thoracotomy; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Rate of Mediastinal Nodal Clearance, Defined as Pathologically Negative N2 Disease in the Final Surgical Resection Specimen or Mediastinoscopy [3 years 9 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Pathologically proven (either histologic or cytologic) diagnosis of stage IIIA or IIIB non-small cell lung cancer; (according to American Joint Committee on Cancer [AJCC] staging, 7th edition) within 4 weeks of registration; the patient should have histologically or cytologically confirmed N2 disease

• Activating mutation in EGFR

• No prior chemotherapy or radiation for lung cancer

• Patients may be potentially resectable or unresectable

• Stage III A or B disease, including no distant metastases- based on following diagnostic workup:

• History/physical examination prior to registration

• Computed tomography (CT) scan of the chest or positron emission tomography (PET) scan within 28 days of study entry

• CT scan of abdomen or magnetic resonance imaging (MRI) of abdomen or PET scan within 28 days of study entry

• An MRI of the brain or head CT scan with contrast within 28 days of study entry

• Total body PET scan within 28 days of study entry

• Mediastinoscopies are highly recommended

• Patients must have measurable or evaluable disease

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Absolute neutrophil count (ANC) >= 1,500 cells/ul

• Platelets >= 100,000 cells/ul

• Hemoglobin >= 9.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= g/dl is acceptable)

• Serum creatinine =< 1.5 x upper limit of normal (ULN)

• Total bilirubin < 2.0 times the institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x the ULN

• Women of childbearing potential must have:

• A negative serum or urine pregnancy test (sensitivity =< 25 IU human chorionic gonadotropin [HCG]/L) within 72 hours prior to the start of study drug administration

• Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy

• Ability to take oral medication

• Patient must sign study specific informed consent prior to study entry

Exclusion Criteria:

• Pleural or pericardial effusion

• Pleural effusions allowed if one of the following conditions are met: 1) negative cytology after adequate sampling by thoracentesis 2) effusion seen on CT scan but not on chest x-ray and deemed too small to tap under CT or ultrasound guidance

• Severe, active co-morbidity, defined as follows:

• Cardiac symptoms; any of the following should be considered for exclusion:

• Uncontrolled angina, congestive heart failure or myocardial infarction (MI) within (6 months)

• Diagnosed congenital long QT syndrome

• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)

• Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 450 msec)

• History of significant bleeding disorder unrelated to cancer, including:

• Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)

• Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)

• Ongoing or recent (=< 3 months) significant gastrointestinal bleeding

• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness

• Men and women who:

• Are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study drug, or women who:

• Have a positive pregnancy test at baseline, or

• Are pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Albert Einstein College of Medicine	Bronx	New York	United States	10461
2	Columbia University Medical Center	New York	New York	United States	10032
3	Weill Cornell Medical College	New York	New York	United States	10065

Sponsors and Collaborators

• Albert Einstein College of Medicine
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Haiying Cheng, Albert Einstein College of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 5, 2014

More Information

Publications

None provided.

• Responsible Party: Haiying Cheng, Principal Investigator, Albert Einstein College of Medicine
• ClinicalTrials.gov Identifier: NCT01857271
• Other Study ID Numbers: 2013-233; NCI-2013-02219; 2013-233-004; 2013-233; P30CA013330
• First Posted: May 20, 2013
• Last Update Posted: Jul 8, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride

Study Results

Participant Flow

Recruitment Details	The patients were enrolled on 11/7/2013, 5/2014, and 9/24/2014.
Pre-assignment Detail	The study was difficult to enroll and eventually terminated/closed.

Arm/Group Title	Treatment (Erlotinib Hydrochloride)
Arm/Group Description	Patients receive erlotinib hydrochloride PO QD for 2 months and then undergo restaging procedures to evaluate for surgery. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies
Period Title: Overall Study
STARTED	3
COMPLETED	2
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (Erlotinib Hydrochloride and Thoracotomy)
Arm/Group Description	Patients receive erlotinib hydrochloride PO QD for 2 months and then undergo thoracotomy. Erlotinib Hydrochloride: Given PO Therapeutic Conventional Surgery: Undergo thoracotomy Laboratory Biomarker Analysis: Correlative studies
Overall Participants	3
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	3 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	2 66.7%
Male	1 33.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 33.3%
Not Hispanic or Latino	1 33.3%
Unknown or Not Reported	1 33.3%

Outcome Measures

1. Primary Outcome

Title	Rate of Mediastinal Nodal Clearance, Defined as Pathologically Negative N2 Disease in the Final Surgical Resection Specimen or Mediastinoscopy
Time Frame	3 years 9 months

Outcome Measure Data

Analysis Population Description

The study was closely prematurely due to poor accrual. No final analysis was performed due to very low number of subjects.

Arm/Group Title	Treatment (Erlotinib Hydrochloride and Thoracotomy)
Arm/Group Description	Patients receive erlotinib hydrochloride PO QD for 2 months and then undergo thoracotomy. Erlotinib Hydrochloride: Given PO Therapeutic Conventional Surgery: Undergo thoracotomy Laboratory Biomarker Analysis: Correlative studies
Measure Participants	0

Adverse Events

Time Frame	6 months
Arm/Group Title	Treatment (Erlotinib Hydrochloride and Thoracotomy)
Arm/Group Description	Patients receive erlotinib hydrochloride PO QD for 2 months and then undergo thoracotomy. Erlotinib Hydrochloride: Given PO Therapeutic Conventional Surgery: Undergo thoracotomy Laboratory Biomarker Analysis: Correlative studies
All Cause Mortality
	Treatment (Erlotinib Hydrochloride and Thoracotomy)
	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)
Serious Adverse Events
	Treatment (Erlotinib Hydrochloride and Thoracotomy)
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Erlotinib Hydrochloride and Thoracotomy)
	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)
Gastrointestinal disorders
Diarrhea	1/3 (33.3%)
Skin and subcutaneous tissue disorders
Rash	1/3 (33.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.