A Study of Erlotinib in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Mutations

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01260181
• Collaborator: (none)
• Enrollment: 30
• Locations: 9
• Arm: 1
• Actual Duration (Months): 78
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This single arm, open-label study will evaluate the efficacy and safety of erlotinib (Tarceva) in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations.

Condition or Disease	Intervention/Treatment	Phase
Non-Squamous Non-Small Cell Lung Cancer	Drug: Erlotinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II, Open-Label Study of Erlotinib (Tarceva®) Treatment in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Present Activating Mutations in the Tyrosine Kinase Domain of the Epidermal Growth Factor Receptor
• Actual Study Start Date: Mar 31, 2011
• Actual Primary Completion Date: Sep 29, 2017
• Actual Study Completion Date: Sep 29, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Erlotinib Participants will receive erlotinib 150 millgrams (mg) orally daily until disease progression.	Drug: Erlotinib; Erlotinib 150 mg tablet will be given orally daily.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Objective Response (Complete Response [CR]/Partial Response [PR]) Based on Computer Tomography (CT) or Magnetic Resonance Imaging (MRI) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 [Baseline up to 5 years (assessed at Baseline, every 8 weeks until disease progression or death or end of treatment period [up to 5 years])]

   Objective response (OR) was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of complete response (CR) and partial response (PR) four at least 4 weeks during treatment. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Secondary Outcome Measures

1. Progression Free Survival (PFS) Based on CT or MRI According to RECIST v 1.1 [Baseline up to 5 years (assessed at Baseline, every 8 weeks until disease progression or death or end of treatment period [up to 5 years])]

   Kaplan Meier estimate of the median PFS was defined as the time at which half of the participants have progressed (progressive disease [PD]) based on RECIST tumor response criteria or died from any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Patients who had not died or progressed at the time of the final analysis were censored at the date of last contact.

2. Overall Survival [Baseline up to 5 years]

   Overall Survival (OS) was defined as the time between the date of randomization and the date of death due to any cause.

3. Percentage of Participants With Adverse Events [Baseline up to 5 years]

   An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

4. Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Mutation in Study Population [Screening (21 days prior to Day 1)]

   Mutations in the EGFR included exon 19 deletion mutations and the single-point substitution mutation L858R in exon 21.

5. Median Time Taken From the First Response Until Disease Progression Based on RECIST v 1.1 as Determined by the Investigator [Baseline up to 5 years (assessed at Baseline, every 8 weeks until disease progression or death or end of treatment period [up to 5 years])]

   The response duration was defined as the time of initial response (complete response (CR) /partial response (PR) whichever is first recorded) until documented disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression was defined as At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Locally advanced or metastatic NSCLC with EGFR mutations

• Measurable disease according to RECIST criteria

• Adequate hematological, renal and liver function

Exclusion Criteria:

• Previous chemotherapy or therapy against EGFR for metastatic disease

• Symptomatic cerebral metastases

• Pre-existing disease of the lung parenchyma such as lung fibrosis, lymphangitic carcinomatosis

• History of another malignancy except for carcinoma in-situ of the cervix, adequately treated basal cell skin carcinoma, or radically treated prostate carcinoma with good prognosis

• Concomitant use of coumarins

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Infante D. Pedro; Servico de Oncologia Medica	Aveiro		Portugal	3814-501
2	Hospital Geral; Servico de Pneumologia	Coimbra		Portugal	3041-801
3	IPO de Lisboa; Servico de Pneumologia	Lisboa		Portugal	1099-023
4	Hospital Santo Antonio dos Capuchos;Servico de Oncologia Medica	Lisboa		Portugal	1150-314
5	Hospital de Santa Maria; Servico de Pneumologia	Lisboa		Portugal	1600
6	Hospital Pulido Valente; Servico de Pneumologia	Lisboa		Portugal	1796-001
7	IPO do Porto; Servico de Oncologia Medica	Porto		Portugal	4200-072
8	Hospital de Sao Joao; Servico de Pneumologia	Porto		Portugal	4200
9	CHVNG/E_Unidade 1; Servico de Pneumologia	Vila Nova De Gaia		Portugal	4434-502

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Statistical Analysis Plan - Mar 28, 2014
• Study Protocol - Feb 12, 2014

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01260181
• Other Study ID Numbers: ML25434; 2010-022509-17
• First Posted: Dec 15, 2010
• Last Update Posted: Oct 31, 2018
• Last Verified: Oct 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Erlotinib
Arm/Group Description	Participants received erlotinib 150 millgrams (mg) orally daily until disease progression.
Period Title: Overall Study
STARTED	30
COMPLETED	29
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Erlotinib
Arm/Group Description	Participants received erlotinib 150 millgrams (mg) orally daily until disease progression.
Overall Participants	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.33 (9.21)
Sex: Female, Male (Count of Participants)
Female	24 80%
Male	6 20%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	30 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Objective Response (Complete Response [CR]/Partial Response [PR]) Based on Computer Tomography (CT) or Magnetic Resonance Imaging (MRI) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
Description	Objective response (OR) was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of complete response (CR) and partial response (PR) four at least 4 weeks during treatment. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	Baseline up to 5 years (assessed at Baseline, every 8 weeks until disease progression or death or end of treatment period [up to 5 years])

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all subjects who are enrolled to the treatment phase of the study, regardless if they completed treatment.

Arm/Group Title	Erlotinib
Arm/Group Description	Participants received erlotinib 150 millgrams (mg) orally daily until disease progression.
Measure Participants	30
Number (95% Confidence Interval) [percentage of participants]	63.3 211%

2. Secondary Outcome

Title	Progression Free Survival (PFS) Based on CT or MRI According to RECIST v 1.1
Description	Kaplan Meier estimate of the median PFS was defined as the time at which half of the participants have progressed (progressive disease [PD]) based on RECIST tumor response criteria or died from any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Patients who had not died or progressed at the time of the final analysis were censored at the date of last contact.
Time Frame	Baseline up to 5 years (assessed at Baseline, every 8 weeks until disease progression or death or end of treatment period [up to 5 years])

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all subjects who are enrolled to the treatment phase of the study, regardless if they completed treatment.

Arm/Group Title	Erlotinib
Arm/Group Description	Participants received erlotinib 150 millgrams (mg) orally daily until disease progression.
Measure Participants	30
Median (95% Confidence Interval) [weeks]	40

3. Secondary Outcome

Title	Overall Survival
Description	Overall Survival (OS) was defined as the time between the date of randomization and the date of death due to any cause.
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all subjects who are enrolled to the treatment phase of the study, regardless if they completed treatment.

Arm/Group Title	Erlotinib
Arm/Group Description	Participants received erlotinib 150 millgrams (mg) orally daily until disease progression.
Measure Participants	30
Median (95% Confidence Interval) [weeks]	83

4. Secondary Outcome

Title	Percentage of Participants With Adverse Events
Description	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

The safety population was identical to the ITT population, which included all participants enrolled in the study.

Arm/Group Title	Erlotinib
Arm/Group Description	Participants received erlotinib 150 millgrams (mg) orally daily until disease progression.
Measure Participants	30
Number [percentage of participants]	29 96.7%

5. Secondary Outcome

Title	Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Mutation in Study Population
Description	Mutations in the EGFR included exon 19 deletion mutations and the single-point substitution mutation L858R in exon 21.
Time Frame	Screening (21 days prior to Day 1)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all subjects who are enrolled to the treatment phase of the study, regardless if they completed treatment.

Arm/Group Title	Erlotinib
Arm/Group Description	Participants received erlotinib 150 millgrams (mg) orally daily until disease progression.
Measure Participants	30
Exon 19 mutation	40 133.3%
Exon 21 mutation	60 200%

6. Secondary Outcome

Title	Median Time Taken From the First Response Until Disease Progression Based on RECIST v 1.1 as Determined by the Investigator
Description	The response duration was defined as the time of initial response (complete response (CR) /partial response (PR) whichever is first recorded) until documented disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression was defined as At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Time Frame	Baseline up to 5 years (assessed at Baseline, every 8 weeks until disease progression or death or end of treatment period [up to 5 years])

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all subjects who are enrolled to the treatment phase of the study, regardless if they completed treatment.

Arm/Group Title	Erlotinib
Arm/Group Description	Participants received erlotinib 150 millgrams (mg) orally daily until disease progression.
Measure Participants	30
Median (95% Confidence Interval) [weeks]	41.5

Adverse Events

Time Frame	5 years
Adverse Event Reporting Description	The safety population was identical to the ITT population, which included all participants enrolled in the study.
Arm/Group Title	Erlotinib
Arm/Group Description	Participants received erlotinib 150 millgrams (mg) orally daily until disease progression.
All Cause Mortality
	Erlotinib
	Affected / at Risk (%)	# Events
Total	4/30 (13.3%)
Serious Adverse Events
	Erlotinib
	Affected / at Risk (%)	# Events
Total	8/30 (26.7%)
Gastrointestinal disorders
Diarrhoea	1/30 (3.3%)
Intestinal Perforation	1/30 (3.3%)
General disorders
Death	1/30 (3.3%)
Infections and infestations
Pneumonia	1/30 (3.3%)
Pelvic Infection	1/30 (3.3%)
Injury, poisoning and procedural complications
Fracture	1/30 (3.3%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	1/30 (3.3%)
Psychiatric disorders
Depression	1/30 (3.3%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	1/30 (3.3%)
Skin and subcutaneous tissue disorders
Rash	1/30 (3.3%)
Other (Not Including Serious) Adverse Events
	Erlotinib
	Affected / at Risk (%)	# Events
Total	29/30 (96.7%)
Blood and lymphatic system disorders
Leukocytosis	2/30 (6.7%)
Eye disorders
Dry Eye	5/30 (16.7%)
Blepharitis	2/30 (6.7%)
Cataract	2/30 (6.7%)
Gastrointestinal disorders
Diarrhoea	15/30 (50%)
Constipation	6/30 (20%)
Nausea	5/30 (16.7%)
Stomatitis	5/30 (16.7%)
Dyspepsia	3/30 (10%)
Abdominal Pain	2/30 (6.7%)
Odynophagia	2/30 (6.7%)
Vomiting	2/30 (6.7%)
General disorders
Fatigue	7/30 (23.3%)
Oedema Peripheral	5/30 (16.7%)
Influenza Like Illness	4/30 (13.3%)
Asthenia	3/30 (10%)
Pain	3/30 (10%)
Infections and infestations
Paronychia	7/30 (23.3%)
Upper Respiratory Tract Infection	7/30 (23.3%)
Eye Infection	2/30 (6.7%)
Conjunctivitis	6/30 (20%)
Investigations
Blood Bilirubin Increased	2/30 (6.7%)
Neutrophil Count Increased	2/30 (6.7%)
Weight Decreased	2/30 (6.7%)
Metabolism and nutrition disorders
Decreased Appetite	8/30 (26.7%)
Hyperglycaemia	3/30 (10%)
Hypomagnesaemia	2/30 (6.7%)
Musculoskeletal and connective tissue disorders
Back Pain	5/30 (16.7%)
Pain in Extremity	3/30 (10%)
Arthralgia	2/30 (6.7%)
Bone Pain	2/30 (6.7%)
Musculoskeletal Chest Pain	2/30 (6.7%)
Neck Pain	2/30 (6.7%)
Nervous system disorders
Headache	4/30 (13.3%)
Dizziness	3/30 (10%)
Psychiatric disorders
Anxiety	4/30 (13.3%)
Depression	3/30 (10%)
Insomnia	3/30 (10%)
Renal and urinary disorders
Pollakiuria	3/30 (10%)
Respiratory, thoracic and mediastinal disorders
Cough	4/30 (13.3%)
Dyspnoea	3/30 (10%)
Haemoptysis	3/30 (10%)
Nasal Congestion	2/30 (6.7%)
Productive Cough	2/30 (6.7%)
Skin and subcutaneous tissue disorders
Dermatitis Acneiform	19/30 (63.3%)
Rash Maculo-Papular	8/30 (26.7%)
Alopecia	5/30 (16.7%)
Acne	2/30 (6.7%)
Erythema	2/30 (6.7%)
Pruritus	5/30 (16.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.