Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00997334
Recruitment Status : Completed
First Posted : October 19, 2009
Results First Posted : April 11, 2017
Last Update Posted : February 23, 2018
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Genentech, Inc.
Information provided by (Responsible Party):
David M. Jackman, MD, Dana-Farber Cancer Institute

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non-small Cell Lung Cancer
Intervention Drug: Erlotinib
Enrollment 60
Recruitment Details Study activated December 2009. Patients enrolled from February 2010 - January 2015
Pre-assignment Details  
Arm/Group Title Erlotinib
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 60
Eligible for Repeat Biopsy 44 [1]
Evaluable 35 [2]
Completed 35
Not Completed 25
Reason Not Completed
still on therapy             12
Adverse Event             3
Patient non-compliance             1
Withdrawal by Subject             3
Death             2
Urgent Palliative Care             2
No lesion amenable             1
Ineligible             1
[1]
Patients who experience disease progression on treatment were eligible for repeat biopsy
[2]
Patients with tissue available for re-biopsy at time of progression
Arm/Group Title Erlotinib
Hide Arm/Group Description Patients receive standard dose of erlotinib 150mg daily with cycle length of 28 days; Patients are treated until disease progression or until unaccepted drug toxicity.
Overall Number of Baseline Participants 60
Hide Baseline Analysis Population Description
The analysis data is comprised of all treated patients
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 60 participants
60
(34 to 90)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants
Female
44
  73.3%
Male
16
  26.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 60 participants
60
 100.0%
Smoking Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants
Never-Smoker
34
  56.7%
Smoker
26
  43.3%
1.Primary Outcome
Title Resistance Mechanism
Hide Description 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.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all evaluable patients.
Arm/Group Title Erlotinib
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 35
Measure Type: Number
Unit of Measure: participants
T790M mutation 23
MET amplification 1
SCLC Transformation 3
Unknown 4
Insufficient Tissue 4
2.Secondary Outcome
Title Progression-Free Survival
Hide Description Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated patients.
Arm/Group Title Erlotinib
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 60
Median (95% Confidence Interval)
Unit of Measure: months
11.1
(9.1 to 14.8)
3.Post-Hoc Outcome
Title Time to Repeat Biopsy
Hide Description Time to repeat biopsy is the duration of time from clinical determination of progressive disease to time of repeat biopsy.
Time Frame At time of removal from study, patients were asked to undergo a repeat biopsy of their progressing or new tumor lesion. Progression follow up was up to 3 years in this study cohort.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all evaluable patients.
Arm/Group Title Erlotinib
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 35
Median (Full Range)
Unit of Measure: days
12
(0 to 97)
4.Post-Hoc Outcome
Title Feasibility Rate
Hide Description Feasibility in this study is defined as the percentage of patients who completed a repeated biopsy per protocol after evidence of disease progression.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all patients eligible for repeat biopsy.
Arm/Group Title Erlotinib
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
79.5
(67.0 to 88.9)
Time Frame Assessed each cycle on treatment up to day 30 post-treatment. Median (range) treatment duration for this study cohort was 10 months (1-62 months).
Adverse Event Reporting Description Serious adverse events (AEs) per protocol are reported. For Other AEs, maximum grade toxicity by type (based on CTCAEv3 which includes coding events as 'Other') for a patient over time including only events with treatment-attribution of possibly, probably or definitely was calculated. A patient appears only once for a given type of toxicity. Patients with reports of multiple toxicities of different types are reported multiple times under the relevant toxicity categories.
 
Arm/Group Title Erlotinib
Hide Arm/Group Description 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.
All-Cause Mortality
Erlotinib
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Erlotinib
Affected / at Risk (%)
Total   5/60 (8.33%) 
Cardiac disorders   
Cardiac - ischemia  1  1/60 (1.67%) 
Cardiac General-Other  1  1/60 (1.67%) 
Gastrointestinal disorders   
Viral Enteritis  1  1/60 (1.67%) 
Hemorrhage, GI - Abdomen NOS  1  1/60 (1.67%) 
Ulcer, colon  1  1/60 (1.67%) 
Infections and infestations   
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Abdomen NOS  1  1/60 (1.67%) 
Metabolism and nutrition disorders   
Dehydration  1  1/60 (1.67%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Death - Disease progression NOS  1  1/60 (1.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAEv3
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Erlotinib
Affected / at Risk (%)
Total   59/60 (98.33%) 
Blood and lymphatic system disorders   
Hemoglobin  1  2/60 (3.33%) 
Hematologic-other  1  5/60 (8.33%) 
Eye disorders   
Dry eye syndrome  1  9/60 (15.00%) 
Eyelid dysfunction  1  1/60 (1.67%) 
Ocular surface disease  1  2/60 (3.33%) 
Tearing  1  1/60 (1.67%) 
Ocular-other  1  11/60 (18.33%) 
Gastrointestinal disorders   
Chelitis  1  1/60 (1.67%) 
Constipation  1  7/60 (11.67%) 
Diarrhea w/o prior colostomy  1  49/60 (81.67%) 
Distention/bloating, abdominal  1  2/60 (3.33%) 
Dry mouth  1  5/60 (8.33%) 
Dyspepsia  1  2/60 (3.33%) 
Muco/stomatitis by exam, oral cavity  1  4/60 (6.67%) 
Muco/stomatitis (symptom) esophagus  1  1/60 (1.67%) 
Muco/stomatitis (symptom) oral cavity  1  1/60 (1.67%) 
Nausea  1  18/60 (30.00%) 
GI-other  1  4/60 (6.67%) 
Upper GI, hemorrhage NOS  1  1/60 (1.67%) 
Abdomen, pain  1  2/60 (3.33%) 
Oral cavity, pain  1  1/60 (1.67%) 
General disorders   
Fatigue  1  26/60 (43.33%) 
Fever w/o neutropenia  1  1/60 (1.67%) 
Rigors/chills  1  1/60 (1.67%) 
Edema limb  1  2/60 (3.33%) 
Pain-other  1  2/60 (3.33%) 
Syndromes-other  1  1/60 (1.67%) 
Infections and infestations   
Infection Gr0-2 neut, conjunctiva  1  1/60 (1.67%) 
Infection Gr0-2 neut, eye NOS  1  1/60 (1.67%) 
Infection Gr0-2 neut, skin  1  1/60 (1.67%) 
Infection Gr0-2 neut, ungual  1  2/60 (3.33%) 
Infection w/ unk ANC conjunctiva  1  1/60 (1.67%) 
Infection w/ unk ANC mucosa  1  1/60 (1.67%) 
Infection w/ unk ANC oral cavity/gums  1  1/60 (1.67%) 
Infection w/ unk ANC ungual (nails)  1  1/60 (1.67%) 
Infection Gr0-2 neut, skin  1  3/60 (5.00%) 
Infection Gr0-2 neut, ungual  1  1/60 (1.67%) 
Infection w/ unk ANC skin (cellulitis)  1  1/60 (1.67%) 
Infection w/ unk ANC vagina  1  2/60 (3.33%) 
Infection-other  1  2/60 (3.33%) 
Investigations   
Leukocytes  1  3/60 (5.00%) 
Neutrophils  1  3/60 (5.00%) 
Weight gain  1  1/60 (1.67%) 
Weight loss  1  9/60 (15.00%) 
Alkaline phosphatase  1  5/60 (8.33%) 
ALT, SGPT  1  8/60 (13.33%) 
AST, SGOT  1  15/60 (25.00%) 
Bilirubin  1  11/60 (18.33%) 
Metabolic/Laboratory-other  1  1/60 (1.67%) 
Metabolism and nutrition disorders   
Anorexia  1  16/60 (26.67%) 
Dehydration  1  3/60 (5.00%) 
Hypomagnesemia  1  1/60 (1.67%) 
Hypokalemia  1  2/60 (3.33%) 
Hyponatremia  1  1/60 (1.67%) 
Musculoskeletal and connective tissue disorders   
Extremity-limb, pain  1  1/60 (1.67%) 
Joint, pain  1  1/60 (1.67%) 
Nervous system disorders   
Taste disturbance  1  8/60 (13.33%) 
Dizziness  1  1/60 (1.67%) 
Neuropathy CN IX pharynx ear tongue  1  1/60 (1.67%) 
Neuropathy CN XII tongue  1  1/60 (1.67%) 
Head/headache  1  1/60 (1.67%) 
Neuropathic, pain  1  1/60 (1.67%) 
Psychiatric disorders   
Insomnia  1  1/60 (1.67%) 
Respiratory, thoracic and mediastinal disorders   
Allergic rhinitis  1  2/60 (3.33%) 
Nose, hemorrhage  1  5/60 (8.33%) 
Cough  1  3/60 (5.00%) 
Nasal cavity/paranasal sinus reaction  1  2/60 (3.33%) 
Pulmonary/Upper Respiratory-other  1  3/60 (5.00%) 
Skin and subcutaneous tissue disorders   
Erythema multiforme  1  5/60 (8.33%) 
Skin breakdown/decubitus ulcer  1  1/60 (1.67%) 
Dry skin  1  36/60 (60.00%) 
Alopecia  1  19/60 (31.67%) 
Hypopigmentation  1  1/60 (1.67%) 
Nail changes  1  13/60 (21.67%) 
Pruritus/itching  1  12/60 (20.00%) 
Rash/desquamation  1  42/60 (70.00%) 
Rash: acne/acneiform  1  19/60 (31.67%) 
Erythema multiforme  1  4/60 (6.67%) 
Skin-other  1  21/60 (35.00%) 
Scalp, pain  1  1/60 (1.67%) 
Vascular disorders   
Flushing  1  1/60 (1.67%) 
Vascular-Other (Specify)  1  1/60 (1.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: David M. Jackman, MD
Organization: Dana-Farber Cancer Institute
Phone: 617.632.3468
EMail: David_Jackman@dfci.harvard.edu
Layout table for additonal information
Responsible Party: David M. Jackman, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00997334    
Other Study ID Numbers: 09-210
NE_OSI4590s ( Other Identifier: Genentech/Roche )
First Submitted: October 16, 2009
First Posted: October 19, 2009
Results First Submitted: January 5, 2017
Results First Posted: April 11, 2017
Last Update Posted: February 23, 2018