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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00556322
First received: November 9, 2007
Last updated: February 4, 2015
Last verified: February 2015
  Purpose

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 Intervention Phase
Non-Small Cell Lung Cancer
Drug: Alimta or Taxotere
Drug: erlotinib [Tarceva]
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Overall survival (OS) was determined from the date of randomization to the date of death irrespective of the cause of death.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Probable Percentage of Participants Remaining Alive at 1 Year [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Probable Percentage of Participants Remaining Alive at 1 Year in the EGFR Positive and Negative Population [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Probable Percentage of Participants Remaining Alive and Progression Free at 6 Months [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Probable Percentage of Participants Remaining Alive and Progression Free at 6 Months in EGFR Positive and Negative Population [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Probable Percentage of Participants Remaining Without Deterioration in Quality of Life at 6 Months as Assessed by FACT-L [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Probable Percentage of Participants With Symptomatic Progression at 6 Months as Assessed by FACT-L [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Probable Percentage of Participants With Deterioration in the TOI at 6 Months as Assessed by FACT-L [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    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.


Enrollment: 424
Study Start Date: March 2006
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00556322

  Hide Study 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, 510080
Guangzhou, China, 510060
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, 135-710
Seoul, Korea, Republic of, 120-752
Seoul, Korea, Republic of, 110-744
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, 94-306
Lodz, Poland, 91-520
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, 420111
Kazan, Russian Federation, 420029
Kirov, Russian Federation
Krasnodar, Russian Federation
Krasnodar, Russian Federation, 350040
Kuzmolovo, Russian Federation, 188663
Moscow, Russian Federation, 105229
Moscow, Russian Federation, 117837
Moscow, Russian Federation, 105203
Moscow, Russian Federation, 115478
Nizhny Novgorod, Russian Federation, 603000
Perm, Russian Federation, 614 066
Smolensk, Russian Federation
Soshi, Russian Federation, 354057
St Petersburg, Russian Federation, 197022
St Petersburg, Russian Federation
St Petersburg, Russian Federation, 191015
St Petersburg, Russian Federation, 195067
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

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00556322     History of Changes
Other Study ID Numbers: BO18602
Study First Received: November 9, 2007
Results First Received: December 3, 2014
Last Updated: February 4, 2015
Health Authority: Slovenia: Ministry of Health

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Docetaxel
Erlotinib
Antimitotic Agents
Antineoplastic Agents
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on April 16, 2015