A Study of Tarceva (Erlotinib) and Standard of Care Chemotherapy in Patients With Advanced, Recurrent, or Metastatic Non-Small Cell Lung Cancer (NSCLC)

• ClinicalTrials.gov Identifier: NCT00556322
• Recruitment Status: Completed
• First Posted: November 12, 2007
• Results First Posted: February 23, 2015
• Last Update Posted: February 23, 2015
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

This 2 arm study will evaluate the efficacy, safety, and pharmacokinetics of Tarceva and that of standard of care chemotherapy in patients with advanced, recurrent, or metastatic NSCLC experiencing disease progression after failure of platinum-based chemotherapy.Eligible patients will be randomized to receive either Tarceva 150mg po daily, or comparator (either Alimta 500mg/m2 every 3 weeks, or Taxotere 75mg/m2 every 3 weeks). The anticipated time on study treatment is until disease progression ,and the target sample size is 500+ individuals.

Condition or disease	Intervention/treatment	Phase
Non-Small Cell Lung Cancer	Drug: Alimta or Taxotere; Drug: erlotinib [Tarceva]	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 424 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Randomized Study to Evaluate the Effect of Tarceva, Compared With Alimta (Pemetrexed) or Taxotere (Docetaxel),on Survival in Patients With Advanced, Recurrent or Metastatic Non-small Cell Lung Cancer Who Have Experienced Disease Progression During Platinum-based Chemotherapy
• Study Start Date: March 2006
• Actual Primary Completion Date: June 2012
• Actual Study Completion Date: June 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1	Drug: erlotinib [Tarceva]; 150mg po daily
Active Comparator: 2	Drug: Alimta or Taxotere; 500mg/m2 / 3 weeks (Alimta) or 75mg/m2 / 3 weeks (Taxotere)

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Who Died (All Participants; Data Cutoff: 07 September 2010) [ Time Frame: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 or Death and Every 12 Weeks until Death or Data Cut off (07 September 2010) up to 52 months ]
   Overall survival (OS) was determined from the date of randomization to the date of death irrespective of the cause of death.
2. Duration of Overall Survival in All Participants (Data Cutoff 07 September 2010) [ Time Frame: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Death or Until Data Cut off (07 September 2010) up to 52 months ]
   OS was determined from the date of randomization to the date of death irrespective of the cause of death. Kaplan-Meier estimates were used for analysis.
3. Probable Percentage of Participants Remaining Alive at 1 Year [ Time Frame: 1 Year ]
   OS was determined from the date of randomization to the date of death irrespective of the cause of death. Kaplan-Meier estimates were used for analysis.

Secondary Outcome Measures :

1. Percentage of Participants Who Died in Epidermal Growth Factor Receptor (EGFR) Positive and Negative Population [ Time Frame: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Death or Until Data Cut off (07 September 2010) up to 52 months ]
   EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by immunohistochemistry (IHC). OS was determined from the date of randomization to the date of death irrespective of the cause of death in EGFR positive and negative populations. Kaplan-Meier estimates were used for analysis.
2. Duration of OS in EGFR Positive and Negative Population [ Time Frame: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Death or Until Data Cut off (07 September 2010) up to 52 months ]
   EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC. OS was determined from the date of randomization to the date of death irrespective of the cause of death in EGFR positive and negative populations. Kaplan-Meier estimates were used for analysis.
3. Probable Percentage of Participants Remaining Alive at 1 Year in the EGFR Positive and Negative Population [ Time Frame: 1 Year ]
   EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC. OS was determined from the date of randomization to the date of death irrespective of the cause of death in EGFR positive and negative populations. Kaplan-Meier estimates were used for analysis.
4. Percentage of Participants With Disease Progression or Death (All Participants; Data Cut Off 07 September 2010) [ Time Frame: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity or Until Data Cut off (07 September 2010) up to 52 months ]
   Tumor response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.0). Progressive Disease was defined as at least a 20 percent (%) increase in the sum of the 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. The primary analysis of PFS used objective progression (RECIST) plus clinical progression (based on relevant clinical findings - if any). A further assessment of PFS was made on objective (radiological) progression. If clinical progression was diagnosed first, the participant was censored at the date of the last tumor assessment, where non-progression was documented.
5. Progression-Free Survival (PFS) in All Participants (Data Cutoff 07 September 2010) [ Time Frame: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity or Until Data Cut off (07 September 2010) up to 52 months ]
   Tumor response was evaluated according to RECIST criteria (version 1.0). Progressive Disease was defined as at least a 20% increase in the sum of 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. PFS was defined as time from randomization to the date of documented disease progression or death, whichever occurred first. Participants without progression were censored at the date of last tumor assessment where non progression was documented. If a participant receives a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy.
6. Probable Percentage of Participants Remaining Alive and Progression Free at 6 Months [ Time Frame: 6 Months ]
   Tumor response was evaluated according to RECIST criteria (version 1.0). Progressive Disease was defined as at least a 20% increase in the sum of 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. Event free estimates were determined using Kaplan-Meier estimates.
7. Percentage of Participants With Disease Progression or Death in EGFR Positive and Negative Population (Data Cut Off 07 September 2010) [ Time Frame: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months ]
   EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC.Tumor response was evaluated according to RECIST criteria (version 1.0). Progressive Disease was defined as At least a 20 % increase in the sum of 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.
8. PFS in EGFR Positive and Negative Population (Data Cutoff 07 September 2010) [ Time Frame: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity or Until Data Cut off (07 September 2010) up to 52 months ]
   EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC. PFS was defined as time from randomization to the date of documented disease progression or death, whichever occurred first in EGFR positive and negative populations. Participants without progression were censored at the date of last tumor assessment where non progression was documented. If a participant receives a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. Kaplan-Meier estimates were used for analysis.
9. Probable Percentage of Participants Remaining Alive and Progression Free at 6 Months in EGFR Positive and Negative Population [ Time Frame: 6 Months ]
   EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC. Tumor response was evaluated according to RECIST criteria (version 1.0). PFS was defined as time from randomization to the date of documented disease progression or death, whichever occurred first in EGFR positive and negative populations. Participants without progression were censored at the date of last tumor assessment where non progression was documented. If a participant receives a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. Event free estimates were determined using Kaplan-Meier estimates.
10. Percentage of Participants Achieving a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator Using RECIST [ Time Frame: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity or Death or up to 52 months ]
    Best overall response was defined as the best response according to RECIST recorded from the date of randomization until disease progression or recurrence. CR: disappearance of all target lesions; PR: reduction by at least 30% of the sum of the longest diameters of each target lesion, taking the initial sum of the longest diameters as a reference; Stable disease (SD): insufficient tumor reduction to define partial response and/or tumor increase less than that necessary to define tumor progression, taking as a reference the smallest sum of the longest diameter since the start of treatment; Progressive Disease (PD): increase by at least 20% in the sum of LD of each target lesion, taking as a reference the smallest sum of the longest diameters, reported since the start of treatment, or appearance of one or more new lesions. 95% Confidence Interval (CI) for one sample binomial using Pearson-Clopper method. Participants with a missing response were considered non-responders.
11. Percentage of Participants With Deterioration in Quality of Life Determined Using Functional Assessment of Cancer Therapy - Lung (FACT-L) [ Time Frame: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months ]
    The FACT-L measures health related QOL and composes of five domains: the four domains (physical well being, emotional well being, social well being, functional well being) from the Functional Assessment of Cancer Treatment-General scale (FACT-G) and the lung cancer subscale (LCS). The FACT-L total score ranges from 0 to 136, higher scores represent better QOL.
12. Time to Deterioration in Quality of Life Using FACT-L [ Time Frame: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months ]
    The FACT-L measures health related QOL and composes of five domains: the four domains (physical well being, emotional well being, social well being, functional well being) from the FACT-G and the LCS. The FACT-L total score ranges from 0 to 136, higher scores represent better QOL. Time to deterioration of QoL or symptom progression is defined as time from randomization until either a clinically meaningful decline from baseline in Total FACT-L or, death on study, whichever occurs first. The clinically meaningful decline that was used to determine deterioration in QoL was ≥6-point decline from baseline. Participants without deterioration in QoL at the time of analysis were censored at the time of the last FACT-L assessment. Kaplan-Meier estimate was used to determine time to event.
13. Probable Percentage of Participants Remaining Without Deterioration in Quality of Life at 6 Months as Assessed by FACT-L [ Time Frame: 6 Months ]
    The FACT-L measures health related QOL and composes of five domains: the four domains (physical well being, emotional well being, social well being, functional well being) from the FACT-G and the LCS. The FACT-L total score ranges from 0 to 136, higher scores represent better QOL. Kaplan Meier estimates were used for analysis.
14. Percentage of Participants With Symptomatic Progression Using FACT-L [ Time Frame: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months ]
    Participants' responses on the FACT-L were scored according to the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system manual. Time to symptom progression is the time from randomization until the earlier of a clinically meaningful decline from baseline in LCS score, or death on study. A change in 2 to 3 points on the LCS is a clinically meaningful change. Meaningful declines in scores as measured by the FACIT instruments have been found to be larger than improvements. Thus, deterioration in disease-related symptoms was defined by the upper bound (3 points) of the range of clinically meaningful change. However, participants who demonstrated early lung cancer progression demonstrated smaller changes from baseline score on the LCS. Therefore, the clinically meaningful decline that was used to determine progression of symptoms in this study was at least 1.5-point decline in LCS score from baseline.
15. Time to Symptomatic Progression Using FACT-L [ Time Frame: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months ]
    Participants' responses on the FACT-L were scored according to FACIT measurement system manual. Time to symptom progression is the time from randomization until the earlier of a clinically meaningful decline from baseline in LCS score, or death on study. A change in 2 to 3 points on the LCS is a clinically meaningful change. Meaningful declines in scores as measured by the FACIT instruments have been found to be larger than improvements. Thus, deterioration in disease-related symptoms was defined by the upper bound (3 points) of the range of clinically meaningful change. However, participants who demonstrated early lung cancer progression demonstrated smaller changes from baseline score on the LCS. Therefore, the clinically meaningful decline that was used to determine progression of symptoms in this study was at least 1.5-point decline in LCS score from baseline. Kaplan Meier estimated were used for analysis.
16. Probable Percentage of Participants With Symptomatic Progression at 6 Months as Assessed by FACT-L [ Time Frame: 6 Months ]
    Participants' responses on the FACT-L were scored according to FACIT measurement system manual. Time to symptom progression is the time from randomization until the earlier of a clinically meaningful decline from baseline in LCS score, or death on study. A change in 2 to 3 points on the LCS is a clinically meaningful change. Meaningful declines in scores as measured by the FACIT instruments have been found to be larger than improvements. Thus, deterioration in disease-related symptoms was defined by the upper bound (3 points) of the range of clinically meaningful change. However, participants who demonstrated early lung cancer progression demonstrated smaller changes from baseline score on the LCS. Therefore, the clinically meaningful decline that was used to determine progression of symptoms in this study was at least 1.5-point decline in LCS score from baseline. Kaplan Meier estimated were used for analysis.
17. Percentage of Participants With Deterioration in the Trial Outcome Index (TOI) [ Time Frame: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months ]
    TOI is defined as the sum of the scores of the Physical Well- Being (PWB), Functional Well-Being (FWB), and LCS of the FACT-L instrument. Trial Outcome Index measures the physical functioning of participants. Time to deterioration in TOI is defined as time from randomization until the earlier of a clinically meaningful decline from baseline in TOI or death on study. The clinically meaningful decline used to determine deterioration in TOI was ≥6-point decline from baseline.
18. Time to Deterioration in the TOI [ Time Frame: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months ]
    TOI is defined as the sum of the scores of the PW, FWB, and LCS of the FACT-L instrument. Trial Outcome Index measures the physical functioning of participants. Time to deterioration in TOI is defined as time from randomization until the earlier of a clinically meaningful decline from baseline in TOI or death on study. The clinically meaningful decline used to determine deterioration in TOI was ≥6- point decline from baseline. Kaplan-Meier estimates were used for analysis.
19. Probable Percentage of Participants With Deterioration in the TOI at 6 Months as Assessed by FACT-L [ Time Frame: 6 Months ]
    TOI is defined as the sum of the scores of the PW, FWB, and LCS of the FACT-L instrument. Trial Outcome Index measures the physical functioning of participants. Time to deterioration in TOI is defined as time from randomization until the earlier of a clinically meaningful decline from baseline in TOI or death on study. The clinically meaningful decline used to determine deterioration in TOI was ≥6-point decline from baseline. Kaplan-Meier estimates were used for analysis.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• adult patients >=18 years of age;
• histologically documented, locally advanced or recurrent or metastatic NSCLC;
• measurable disease;
• disease progression during 1-4 cycles of platinum-based chemotherapy.

Exclusion Criteria:

• any other malignancies within the last 5 years;
• unstable systemic disease.

Contacts and Locations

Locations

Australia, New South Wales

St. Leonards, New South Wales, Australia, 2065

Waratah, New South Wales, Australia, 2298

Australia, South Australia

Adelaide, South Australia, Australia, 5041

Australia, Victoria

East Bentleigh, Victoria, Australia, VIC 3165

Fitzroy, Victoria, Australia, 3065

Geelong, Victoria, Australia, 3220

Melbourne, Victoria, Australia, 3084

Austria

Innsbruck, Austria, 6020

Klagenfurt, Austria, 9010

Wien, Austria, 1140

Wien, Austria, 1145

Belgium

Antwerpen, Belgium, 2020

Canada, Manitoba

Winnipeg, Manitoba, Canada, R3E 0V9

Canada, Ontario

Oshawa, Ontario, Canada, L1G 2B9

Sault Ste Marie, Ontario, Canada, P6A 2C4

Toronto, Ontario, Canada, M4C 3E7

Canada, Quebec

Laval, Quebec, Canada, H7M 3L9

Montreal, Quebec, Canada, H4J 1C5

Chile

Santiago, Chile, 0000

China

Beijing, China, 100730

Guangzhou, China, 510060

Guangzhou, China, 510080

Shanghai, China, 200032

Czech Republic

Ceské Budejovice, Czech Republic, 370 87

Olomouc, Czech Republic, 775 20

Plzen, Czech Republic, 305 99

Denmark

Herlev, Denmark, 2730

Odense, Denmark, 5000

France

Bayonne, France, 64100

Brest, France, 29200

Clermont-ferrand, France, 63003

Dijon, France, 21079

Le Mans, France, 72037

Lille, France, 59020

Limoges, France, 87042

Paris, France, 75674

PAU, France, 64046

Toulouse, France, 31400

Vandoeuvre-les-nancy, France, 54511

Germany

Bad Berka, Germany, 99437

Bochum, Germany, 44791

Halle (Saale), Germany, 06120

Herne, Germany, 44625

Neuruppin, Germany, 16816

Villingen-Schwenningen, Germany, 78052

Greece

Athens, Greece, 11527

Athens, Greece, 14564

Heraklion, Greece, 71110

Hungary

Budapest, Hungary, 1125

Budapest, Hungary, 1529

Deszk, Hungary, 6772

Nyíregyháza, Hungary, 4400

Pecs, Hungary, 7635

Szombathely, Hungary, 9700

Torokbalint, Hungary, 2045

Italy

Bologna, Emilia-Romagna, Italy, 40139

Roma, Lazio, Italy, 00168

Ancona, Marche, Italy

Korea, Republic of

Daegu, Korea, Republic of, 700-712

Seoul, Korea, Republic of, 110-744

Seoul, Korea, Republic of, 120-752

Seoul, Korea, Republic of, 135-710

Seoul, Korea, Republic of, 138-736

Seoul, Korea, Republic of, 139-709

Suwon, Korea, Republic of

Lithuania

Kaunas, Lithuania

Klaipeda, Lithuania, 92288

Vilnius, Lithuania, 08660

Malaysia

Kuala Lumpur, Malaysia, 59100

Penang, Malaysia, 11200

New Zealand

Auckland, New Zealand, 1009

Christchurch, New Zealand

Poland

Lodz, Poland, 91-520

Lodz, Poland, 94-306

Otwock, Poland, 05-400

Romania

Bucuresti, Romania, 022328

Cluj Napoca, Romania, 400015

Iasi, Romania, 6600

Timisoara, Romania, 1900

Russian Federation

Arkhangelsk, Russian Federation, 163045

Balashikha, Russian Federation, 143900

Chelyabinsk, Russian Federation, 454 087

Kazan, Russian Federation, 420029

Kazan, Russian Federation, 420111

Kirov, Russian Federation

Krasnodar, Russian Federation, 350040

Krasnodar, Russian Federation

Kuzmolovo, Russian Federation, 188663

Moscow, Russian Federation, 105203

Moscow, Russian Federation, 105229

Moscow, Russian Federation, 115478

Moscow, Russian Federation, 117837

Nizhny Novgorod, Russian Federation, 603000

Perm, Russian Federation, 614 066

Smolensk, Russian Federation

Soshi, Russian Federation, 354057

St Petersburg, Russian Federation, 191015

St Petersburg, Russian Federation, 195067

St Petersburg, Russian Federation, 197022

St Petersburg, Russian Federation

Yaroslavl, Russian Federation, 150054

Slovakia

Banska Bystrica, Slovakia, 975 17

Bratislava, Slovakia, 825 56

Nitra, Slovakia, 949 88

Poprad, Slovakia, 058 87

Slovenia

Golnik, Slovenia

Ljubljana, Slovenia, 1000

Maribor, Slovenia

South Africa

Durban, South Africa, 4091

Johannesburg, South Africa, 2196

Pretoria, South Africa, 0001

Spain

Oviedo, Asturias, Spain, 33006

Santander, Cantabria, Spain, 39008

La Coruña, Spain, 15006

Zaragoza, Spain, 50009

Ukraine

Kharkov, Ukraine, 61024

Uzhgorod, Ukraine, 88000

Zaporozhye, Ukraine, 69104

United Kingdom

Chelmsford, United Kingdom, CM1 7ET

Dundee, United Kingdom, DD1 9SY

Leicester, United Kingdom, LE1 5WW

Plymouth, United Kingdom, PL6 8DH

Venezuela

Caracas, Venezuela, 1062

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ciuleanu T, Stelmakh L, Cicenas S, Miliauskas S, Grigorescu AC, Hillenbach C, Johannsdottir HK, Klughammer B, Gonzalez EE. Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Lancet Oncol. 2012 Mar;13(3):300-8. doi: 10.1016/S1470-2045(11)70385-0. Epub 2012 Jan 24.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00556322
• Other Study ID Numbers: BO18602
• First Posted: November 12, 2007
• Results First Posted: February 23, 2015
• Last Update Posted: February 23, 2015
• Last Verified: February 2015

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Erlotinib Hydrochloride; Docetaxel; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators