A Study of Tarceva (Erlotinib) to Compare Two Different Doses in in Currently Smoking Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (CURRENTS)

• ClinicalTrials.gov Identifier: NCT01183858
• Recruitment Status: Completed
• First Posted: August 18, 2010
• Results First Posted: February 23, 2015
• Last Update Posted: August 19, 2015
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer
• Intervention: Drug: Erlotinib [Tarceva]
• Enrollment: 315

Participant Flow

Recruitment Details
Pre-assignment Details	315 participants were randomized. 313 participants were included in the Intent-to -treat (ITT) population. The ITT population excluded 2 randomized participants: 1 participant randomized in error and 1 participant with missing source data.

Arm/Group Title	Erlotinib 150 mg	Erlotinib 300 mg
Arm/Group Description	Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg single daily oral dose until disease progression.
Period Title: Overall Study
Started	154	159
Safety Population	154	158
Completed	1	3
Not Completed	153	156
Reason Not Completed
Death not related to Progressive Disease	5	6
Adverse Event	14	11
Investigator's Decision	0	3
Insufficient Therapeutic Response	2	0
Refused Treatment	1	4
Withdrew Consent	4	4
Discontinued Smoking	3	1
Protocol Violation	1	0
Administrative/Other	6	6
Progressive Disease	112	115
Death related to Progressive Disease	4	5
Lost to Follow-up	1	1

Baseline Characteristics

Arm/Group Title		Erlotinib 150 mg	Erlotinib 300 mg	Total
Arm/Group Description		Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg single daily oral dose until disease progression.	Total of all reporting groups
Overall Number of Baseline Participants		154	159	313
Baseline Analysis Population Description		Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	154 participants	159 participants	313 participants
		59.7 (9.25)	59.2 (9.14)	59.4 (9.18)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	154 participants	159 participants	313 participants
	Female	34 22.1%	35 22.0%	69 22.0%
	Male	120 77.9%	124 78.0%	244 78.0%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS is defined as the time from randomization to the date of first occurrence of disease progression or death. For target lesions, Progressive Disease (PD) was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.
Time Frame	Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 Months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.

Arm/Group Title	Erlotinib 150 mg	Erlotinib 300 mg
Arm/Group Description:	Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg single daily oral dose until disease progression.
Overall Number of Participants Analyzed	154	159
Median (95% Confidence Interval); Unit of Measure: weeks
	6.86; (6.29 to 12.00)	7.00; (6.29 to 11.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erlotinib 150 mg, Erlotinib 300 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.671
	Comments	Unstratified analysis.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.33
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Progression-Free Survival (PFS) at the End of Study
Description	PFS is defined as the time from randomization to the date of first occurrence of disease progression or death. For target lesions, Progressive Disease (PD) was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.
Time Frame	Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.

Arm/Group Title	Erlotinib 150 mg	Erlotinib 300 mg
Arm/Group Description:	Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg single daily oral dose until disease progression.
Overall Number of Participants Analyzed	154	159
Median (95% Confidence Interval); Unit of Measure: weeks
	6.86; (6.29 to 12.00)	7.00; (6.29 to 11.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erlotinib 150 mg, Erlotinib 300 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.625
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.33
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Overall Survival (OS)
Description	OS defined as the time from randomization to the date of death due to any cause.
Time Frame	Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.

Arm/Group Title	Erlotinib 150 mg	Erlotinib 300 mg
Arm/Group Description:	Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg single daily oral dose until disease progression.
Overall Number of Participants Analyzed	154	159
Median (95% Confidence Interval); Unit of Measure: months
	6.77; (5.65 to 8.77)	6.83; (5.39 to 8.48)

4. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	Tumor response was assessed by the investigator using computer tomography (CT) or magnetic resonance imaging (MRI) scans according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A participant was defined as a responder if they sustained a complete response (CR) or partial response (PR) for at least 4 weeks during randomized treatment (confirmed response). Patients with no tumor assessment after the start of study treatment were to be considered as non-responders. The percentage of participants in each best response category is presented.
Time Frame	Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.

Arm/Group Title	Erlotinib 150 mg	Erlotinib 300 mg
Arm/Group Description:	Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg single daily oral dose until disease progression.
Overall Number of Participants Analyzed	154	159
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Complete Response	0.0; (0.0 to 0.0)	0.0; (0.0 to 0.0)
Partial Response	7.1; (3.6 to 12.4)	2.5; (0.7 to 6.3)
Stable Disease	33.1; (25.8 to 41.1)	34.0; (26.6 to 41.9)
Progressive Disease	44.8; (36.8 to 53.0)	45.9; (38.0 to 54.0)
Not Evaluable	14.9; (9.7 to 21.6)	17.6; (12.0 to 24.4)

5. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	Tumor response was assessed by the investigator using computer tomography (CT) or magnetic resonance imaging (MRI) scans. Disease control rates were measured according to RECIST version 1.1 criteria. A participant was defined as having controlled disease if they sustained a Complete Response (CR) or Partial Response (PR) for at least 4 weeks during randomized treatment (confirmed response), or Stable Disease (SD) for at least 6 weeks. Patients with no tumor assessment after the start of study treatment were considered as having uncontrolled disease. The percentage of participants with Disease Control is presented.
Time Frame	Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.

Arm/Group Title	Erlotinib 150 mg	Erlotinib 300 mg
Arm/Group Description:	Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg single daily oral dose until disease progression.
Overall Number of Participants Analyzed	154	159
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	40.3; (32.4 to 48.5)	36.5; (29.0 to 44.5)

6. Secondary Outcome

Title	Time to Progression (TTP)
Description	Tumor response was assessed by the investigator using computer tomography (CT) or magnetic resonance imaging (MRI) scans according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. Time to progression (TTP) in weeks was defined as the time from randomization to the date of disease progression. Participants without event were censored at the date of the last tumor assessment when the patient was known to be progression free.
Time Frame	Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.

Arm/Group Title	Erlotinib 150 mg	Erlotinib 300 mg
Arm/Group Description:	Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg single daily oral dose until disease progression.
Overall Number of Participants Analyzed	154	159
Median (95% Confidence Interval); Unit of Measure: weeks
	9.86; (6.43 to 12.14)	9.14; (6.43 to 12.00)

7. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) at the End of the Study
Description	An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. Adverse Events in the following categories are presented: Adverse Events, Serious Adverse Events, AEs leading to withdrawal from treatment and AEs leading to death.
Time Frame	Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months)

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who received at least one dose of study drug.

Arm/Group Title	Erlotinib 150 mg	Erlotinib 300 mg
Arm/Group Description:	Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg single daily oral dose until disease progression.
Overall Number of Participants Analyzed	154	158
Measure Type: Number; Unit of Measure: participants
Adverse Events (AEs)	130	141
Serious Adverse Events	29	35
AEs leading to withdrawal	18	15
AEs leading to death	12	13

8. Secondary Outcome

Title	Overall Survival (OS) at the End of Study
Description	OS defined as the time from randomization to the date of death due to any cause.
Time Frame	Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.

Arm/Group Title	Erlotinib 150 mg	Erlotinib 300 mg
Arm/Group Description:	Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg single daily oral dose until disease progression.
Overall Number of Participants Analyzed	154	159
Median (95% Confidence Interval); Unit of Measure: months
	7.00; (5.65 to 8.84)	6.90; (5.62 to 8.64)

Adverse Events

Time Frame	Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months)
Adverse Event Reporting Description	Safety population: All participants who received at least 1 dose of study drug.
Arm/Group Title	Erlotinib 150 mg	Erlotinib 300 mg
Arm/Group Description	Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg single daily oral dose until disease progression.
All-Cause Mortality
	Erlotinib 150 mg	Erlotinib 300 mg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Erlotinib 150 mg	Erlotinib 300 mg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	29/154 (18.83%)	35/158 (22.15%)
Blood and lymphatic system disorders
Febrile neutropenia † 1	1/154 (0.65%)	0/158 (0.00%)
Cardiac disorders
Myocardial infarction † 1	1/154 (0.65%)	3/158 (1.90%)
Arteriospasm coronary † 1	0/154 (0.00%)	1/158 (0.63%)
Cardiac failure † 1	1/154 (0.65%)	0/158 (0.00%)
Intracardiac thrombus † 1	0/154 (0.00%)	1/158 (0.63%)
Right ventricular failure † 1	1/154 (0.65%)	0/158 (0.00%)
Gastrointestinal disorders
Diarrhoea † 1	1/154 (0.65%)	2/158 (1.27%)
Haematemesis † 1	1/154 (0.65%)	1/158 (0.63%)
Vomiting † 1	0/154 (0.00%)	2/158 (1.27%)
Duodenal ulcer † 1	0/154 (0.00%)	1/158 (0.63%)
Inguinal hernia † 1	0/154 (0.00%)	1/158 (0.63%)
Nausea † 1	0/154 (0.00%)	1/158 (0.63%)
Stomatitis † 1	0/154 (0.00%)	1/158 (0.63%)
Upper gastrointestinal haemorrhage † 1	0/154 (0.00%)	1/158 (0.63%)
General disorders
General physical health deterioration † 1	1/154 (0.65%)	3/158 (1.90%)
Fatigue † 1	1/154 (0.65%)	1/158 (0.63%)
Death † 1	1/154 (0.65%)	0/158 (0.00%)
Mucosal inflammation † 1	1/154 (0.65%)	0/158 (0.00%)
Sudden death † 1	0/154 (0.00%)	1/158 (0.63%)
Hepatobiliary disorders
Hepatic failure † 1	1/154 (0.65%)	0/158 (0.00%)
Infections and infestations
Pneumonia † 1	6/154 (3.90%)	3/158 (1.90%)
Respiratory tract infection † 1	0/154 (0.00%)	3/158 (1.90%)
Anal abscess † 1	0/154 (0.00%)	1/158 (0.63%)
Lower respiratory tract infection bacterial † 1	0/154 (0.00%)	1/158 (0.63%)
Lung infection † 1	1/154 (0.65%)	0/158 (0.00%)
Septic shock † 1	1/154 (0.65%)	0/158 (0.00%)
Injury, poisoning and procedural complications
Femur fracture † 1	0/154 (0.00%)	1/158 (0.63%)
Hip fracture † 1	0/154 (0.00%)	1/158 (0.63%)
Overdose † 1	1/154 (0.65%)	0/158 (0.00%)
Metabolism and nutrition disorders
Dehydration † 1	2/154 (1.30%)	1/158 (0.63%)
Musculoskeletal and connective tissue disorders
Back pain † 1	1/154 (0.65%)	1/158 (0.63%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer † 1	1/154 (0.65%)	0/158 (0.00%)
Pericardial effusion malignant † 1	1/154 (0.65%)	0/158 (0.00%)
Nervous system disorders
Cerebral infarction † 1	1/154 (0.65%)	0/158 (0.00%)
Haemorrhage intracranial † 1	0/154 (0.00%)	1/158 (0.63%)
Hypoxic-ischaemic encephalopathy † 1	0/154 (0.00%)	1/158 (0.63%)
Ischaemic stroke † 1	0/154 (0.00%)	1/158 (0.63%)
Neuralgia † 1	0/154 (0.00%)	1/158 (0.63%)
Somnolence † 1	1/154 (0.65%)	0/158 (0.00%)
Renal and urinary disorders
Renal failure † 1	1/154 (0.65%)	0/158 (0.00%)
Renal failure acute † 1	1/154 (0.65%)	0/158 (0.00%)
Renal failure chronic † 1	1/154 (0.65%)	0/158 (0.00%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	3/154 (1.95%)	1/158 (0.63%)
Respiratory failure † 1	0/154 (0.00%)	2/158 (1.27%)
Acute respiratory failure † 1	1/154 (0.65%)	0/158 (0.00%)
Chronic obstructive pulmonary disease † 1	1/154 (0.65%)	0/158 (0.00%)
Haemoptysis † 1	0/154 (0.00%)	1/158 (0.63%)
Hydropneumothorax † 1	1/154 (0.65%)	0/158 (0.00%)
Pneumonitis † 1	0/154 (0.00%)	1/158 (0.63%)
Pneumothorax † 1	0/154 (0.00%)	1/158 (0.63%)
Pulmonary haemorrhage † 1	0/154 (0.00%)	1/158 (0.63%)
Vascular disorders
Deep vein thrombosis † 1	0/154 (0.00%)	1/158 (0.63%)
Peripheral ischaemia † 1	0/154 (0.00%)	1/158 (0.63%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (16.1)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Erlotinib 150 mg	Erlotinib 300 mg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	115/154 (74.68%)	128/158 (81.01%)
Blood and lymphatic system disorders
Anaemia † 1	6/154 (3.90%)	8/158 (5.06%)
Gastrointestinal disorders
Diarrhoea † 1	29/154 (18.83%)	46/158 (29.11%)
Nausea † 1	20/154 (12.99%)	17/158 (10.76%)
Vomiting † 1	13/154 (8.44%)	14/158 (8.86%)
Constipation † 1	9/154 (5.84%)	11/158 (6.96%)
Dyspepsia † 1	3/154 (1.95%)	8/158 (5.06%)
Abdominal pain upper † 1	1/154 (0.65%)	8/158 (5.06%)
General disorders
Fatigue † 1	21/154 (13.64%)	26/158 (16.46%)
Chest pain † 1	7/154 (4.55%)	14/158 (8.86%)
Asthenia † 1	9/154 (5.84%)	12/158 (7.59%)
Pain † 1	8/154 (5.19%)	5/158 (3.16%)
Investigations
Weight decreased † 1	7/154 (4.55%)	15/158 (9.49%)
Metabolism and nutrition disorders
Decreased appetite † 1	26/154 (16.88%)	32/158 (20.25%)
Musculoskeletal and connective tissue disorders
Pain in extremity † 1	3/154 (1.95%)	8/158 (5.06%)
Back pain † 1	8/154 (5.19%)	6/158 (3.80%)
Nervous system disorders
Headache † 1	9/154 (5.84%)	2/158 (1.27%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	26/154 (16.88%)	19/158 (12.03%)
Cough † 1	23/154 (14.94%)	19/158 (12.03%)
Skin and subcutaneous tissue disorders
Rash † 1	43/154 (27.92%)	75/158 (47.47%)
Dry skin † 1	13/154 (8.44%)	17/158 (10.76%)
Pruritus † 1	8/154 (5.19%)	16/158 (10.13%)
Dermatitis acneiform † 1	11/154 (7.14%)	9/158 (5.70%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (16.1)

Limitations and 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.

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.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 800-821-8590
• EMail: genetech@druginfo.com

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01183858
• Other Study ID Numbers: MO22162; 2010-018476-24 ( EudraCT Number )
• First Submitted: August 16, 2010
• First Posted: August 18, 2010
• Results First Submitted: February 5, 2015
• Results First Posted: February 23, 2015
• Last Update Posted: August 19, 2015