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A Study of First-line Maintenance Erlotinib Versus Erlotinib at Disease Progression in Participants With Advanced Non-Small Cell Lung Cancer (NSCLC) Who Have Not Progressed Following Platinum-Based Chemotherapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01328951
First received: April 4, 2011
Last updated: March 2, 2016
Last verified: March 2016
  Purpose
This double-blind, placebo-controlled study will evaluate the benefit of first-line maintenance erlotinib (Tarceva) versus erlotinib at the time of disease progression in participants with advanced NSCLC who have not progressed following 4 cycles of platinum based-chemotherapy and whose tumor does not harbor an epidermal growth factor receptor (EGFR)-activating mutation. Participants will be randomized to receive either erlotinib 150 milligrams (mg) orally (PO) once daily or placebo. Participants who progress on placebo will receive erlotinib 150 mg PO once daily as second-line therapy, and those who progress on erlotinib may switch to a non-investigational, second-line chemotherapy. Treatments will continue until disease progression, death, or unacceptable toxicity. Participants may also be entered into a final Survival Follow-Up (SFU) period upon treatment discontinuation.

Condition Intervention Phase
Non-Squamous Non-Small Cell Lung Cancer
Drug: Placebo
Drug: Erlotinib
Drug: Second-Line Chemotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Phase III Study of First-Line Maintenance Tarceva Versus Tarceva at the Time of Disease Progression in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) Who Have Not Progressed Following 4 Cycles of 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 During the Overall Study [ Time Frame: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP; per local standards during OLP; then every 12 weeks during SFU until death) ] [ Designated as safety issue: No ]
    Participants were followed for survival until death or premature withdrawal. The percentage of participants who died during the Overall Study (BP, OLP, or SFU) was calculated.

  • Overall Survival (OS) as Median Time to Event During the Overall Study [ Time Frame: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP; per local standards during OLP; then every 12 weeks during SFU until death) ] [ Designated as safety issue: No ]
    Participants were followed for survival until death or premature withdrawal. OS was defined as the interval between date of randomization and date of death from any cause. Median time to event during the Overall Study (BP, OLP, or SFU) was estimated using the Kaplan-Meier method and expressed in months.

  • Percentage of Participants Event-Free (Alive) at 1 Year During the Overall Study [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
    Participants were followed for survival until death or premature withdrawal. The percentage of participants event-free (i.e., still alive) at 1 year during the Overall Study was calculated.


Secondary Outcome Measures:
  • Percentage of Participants Who Died or Experienced Disease Progression During Blinded Treatment [ Time Frame: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP) ] [ Designated as safety issue: No ]
    Tumor response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Disease progression was defined as a greater than or equal to (≥) 20 percent (%) and ≥5-millimeter (mm) increase in the sum of target lesion diameters in reference to the smallest sum on study and/or substantial worsening in non-target disease. The percentage of participants who died or experienced disease progression during the BP was calculated.

  • Progression-Free Survival (PFS) as Median Time to Event During Blinded Treatment [ Time Frame: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP) ] [ Designated as safety issue: No ]
    Tumor response was evaluated using RECIST version 1.1. Disease progression was defined as a ≥20% and ≥5-mm increase in the sum of target lesion diameters in reference to the smallest sum on study and/or substantial worsening in non-target disease. PFS was defined as the interval between date of randomization and date of first documented death or disease progression. Median time to event during the BP was estimated using the Kaplan-Meier method and expressed in weeks.

  • Percentage of Participants Event-Free (Alive and No Disease Progression) at 6 Months During Blinded Treatment [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
    Tumor response was evaluated using RECIST version 1.1. Disease progression was defined as a ≥20% and ≥5-mm increase in the sum of target lesion diameters in reference to the smallest sum on study and/or substantial worsening in non-target disease. The percentage of participants event-free (i.e., still alive and without disease progression) at 6 months during the BP was calculated.

  • Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to RECIST During Blinded Treatment [ Time Frame: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP) ] [ Designated as safety issue: No ]
    Tumor response was evaluated using RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and short-axis reduction to less than (<) 10 mm of any pathological lymph nodes. PR was defined as a ≥30% decrease in the sum of target lesion diameters in reference to the Baseline sum. The percentage of participants with a best overall response of either CR or PR (i.e., the objective response rate [ORR]) during the BP was calculated, and corresponding 95% CI was constructed using the Pearson-Clopper method.

  • Percentage of Participants by Best Overall Response According to RECIST During Blinded Treatment [ Time Frame: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP) ] [ Designated as safety issue: No ]
    Tumor response was evaluated using RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as a ≥30% decrease in the sum of target lesion diameters in reference to the Baseline sum. Stable disease (SD) was defined as neither sufficient shrinkage in target lesions to qualify for PR nor sufficient growth to qualify for disease progression. Disease progression (progressive disease/PD) was defined as a ≥20% and ≥5-mm increase in the sum of target lesion diameters in reference to the smallest sum on study and/or substantial worsening in non-target disease. The percentage of participants with each level of best tumor response during the BP was calculated, and corresponding 95% CI was constructed using the Pearson-Clopper method.

  • Percentage of Participants With CR, PR, or SD According to RECIST During Blinded Treatment [ Time Frame: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP) ] [ Designated as safety issue: No ]
    Tumor response was evaluated using RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as a ≥30% decrease in the sum of target lesion diameters in reference to the Baseline sum. SD was defined as neither sufficient shrinkage in target lesions to qualify for PR nor sufficient growth to qualify for disease progression. The percentage of participants with a best overall response of CR, PR, or SD (i.e., the disease control rate [DCR]) during the BP was calculated, and corresponding 95% CI was constructed using the Pearson-Clopper method.


Enrollment: 643
Study Start Date: September 2011
Study Completion Date: January 2016
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Early Erlotinib
Participants will receive blinded erlotinib as 150 mg PO once daily in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrate disease progression may be unblinded to receive an approved second-line therapy (but not EGFR targeted therapies) until disease progression, death, or unacceptable toxicity. Participants may be observed during a final SFU period after discontinuation from study treatment.
Drug: Erlotinib
Erlotinib will be administered as 150 mg PO once daily until disease progression, death, or unacceptable toxicity, as first-line maintenance or as second-line therapy for those who progress while receiving placebo.
Other Name: Tarceva
Drug: Second-Line Chemotherapy
Participants who progress on first-line maintenance erlotinib may receive an approved second-line therapy (but not EGFR targeted therapies) until disease progression, death, or unacceptable toxicity. The selected chemotherapy will be non-investigational and chosen at the discretion of the Investigator.
Placebo Comparator: Late Erlotinib
Participants will receive blinded placebo tablets PO once daily in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrate disease progression may be unblinded to receive second-line erlotinib as 150 mg PO once daily until disease progression, death, or unacceptable toxicity. Participants may be observed during a final SFU period after discontinuation from study treatment.
Drug: Placebo
Placebo will be administered PO once daily as first-line maintenance until disease progression, death, or unacceptable toxicity.
Drug: Erlotinib
Erlotinib will be administered as 150 mg PO once daily until disease progression, death, or unacceptable toxicity, as first-line maintenance or as second-line therapy for those who progress while receiving placebo.
Other Name: Tarceva

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults greater than or equal to (≥) 18 years of age, or legal age of consent if greater than 18
  • Advanced or recurrent (Stage IIIB) or metastatic (Stage IV) NSCLC
  • Completion of 4 cycles of platinum-based chemotherapy without progression (end of last chemotherapy cycle less than or equal to [≤] 28 days prior to randomization)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Exclusion Criteria:

  • Prior exposure to agents directed at human epidermal growth factor receptor (HER) axis (e.g. erlotinib, gafitinib, cetuximab)
  • Participants whose tumors harbor an EGFR-activating mutation
  • Prior chemotherapy or therapy with systemic anti-neoplastic therapy for advanced disease before Screening
  • Use of pemetrexed in maintenance setting (pemetrexed allowed during the chemotherapy run-in)
  • Participants who have undergone complete tumor resection after responding to the platinum-based chemotherapy during the Screening phase
  • Any other malignancies within 5 years, except for curatively resected carcinoma in situ of the cervix, basal or squamous cell skin cancer, ductal carcinoma in situ, or organ-confined prostate cancer
  • Central nervous system (CNS) metastases or spinal cord compression that has not been definitely treated with surgery and/or radiation, or treated CNS metastases or spinal cord compression without stable disease for ≥2 months
  • Human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection
  • Any inflammatory changes of the surface of the eye
  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: NCT01328951

  Hide Study Locations
Locations
United States, California
Gilroy, California, United States, 95020
United States, District of Columbia
Washington, District of Columbia, United States, 20010
United States, Missouri
Kansas City, Missouri, United States, 64132
United States, Montana
Missoula, Montana, United States, 59802
United States, New Hampshire
Lebanon, New Hampshire, United States, 03756
United States, Ohio
Dayton, Ohio, United States, 45420
United States, Tennessee
Chattanooga, Tennessee, United States, 37404
United States, Washington
Spokane, Washington, United States, 99218
Tacoma, Washington, United States, 98405
Brazil
Belo Horizonte, MG, Brazil, 30150-281
Ijuí, RO, Brazil, 98700-000
Lajeado, RS, Brazil, 95900-000
Porto Alegre, RS, Brazil, 90020-090
Porto Alegre, RS, Brazil, 90035-003
Porto Alegre, RS, Brazil, 90430-090
Porto Alegre, RS, Brazil, 90470340
Florianopolis, SC, Brazil, 88034-000
Santo André, SP, Brazil, 09060-650
Bulgaria
Gabrovo, Bulgaria, 5300
Haskovo, Bulgaria, 6300
Plovdiv, Bulgaria, 4004
Ruse, Bulgaria, 7000
Sofia, Bulgaria, 1233
Sofia, Bulgaria, 1303
Sofia, Bulgaria, 1527
Sofia, Bulgaria, 1606
Sofia, Bulgaria, 1756
Sofia, Bulgaria, 1784
Varna, Bulgaria, 9010
Canada, Ontario
Windsor, Ontario, Canada, N8W 2X3
Canada, Quebec
Montreal, Quebec, Canada, H3T 1E2
Canada, Saskatchewan
Regina, Saskatchewan, Canada, S4T 7T1
Canada
Quebec, Canada, G1V 4G5
China
Beijing, China, 100142
Beijing, China, 100730
Changchun, China, 130012
Fuzhou, China, 350014
Guangzhou, China, 510515
Guangzhou, China
Harbin, China, 150081
Shanghai, China, 200030
Shanghai, China, 200433
Shantou, China, 515041
Shenyang, China, 110001
Suzhou, China, 215004
Tianjin, China, 300060
Wuhan, China, 430071
Xi'an, China, 710061
Czech Republic
Ceske Budejovice, Czech Republic, 370 87
Jindrichuv Hradec, Czech Republic, 377 01
Nymburk, Czech Republic, 288 01
Ostrava - Poruba, Czech Republic, 708 52
Praha 8, Czech Republic, 180 81
Praha, Czech Republic, 150 06
Tabor, Czech Republic, 390 03
France
Bayonne, France, 64109
Compiegne, France, 60321
Gap, France, 05007
Libourne, France, 33505
Lille, France, 59020
Nantes, France, 44202
St Brieuc, France, 22027
Villefranche-sur-Saone, France, 69655
Hungary
Budapest, Hungary, 1121
Budapest, Hungary, 1122
Budapest, Hungary, 1125
Budapest, Hungary, 1145
Deszk, Hungary, 6772
Farkasgyepu, Hungary, 8582
Gyor, Hungary, 9024
Gyula, Hungary, 5703
Matrahaza, Hungary, 3233
Miskolc, Hungary, 3526
Szolnok, Hungary, 5000
Székesfehérvár, Hungary, 8000
Torokbalint, Hungary, 2045
Zalaegerszeg, Hungary, 8900
Italy
Avellino, Campania, Italy, 83100
Bologna, Emilia-Romagna, Italy, 40138
Parma, Emilia-Romagna, Italy, 43100
Roma, Lazio, Italy, 00144
Roma, Lazio, Italy, 00151
Roma, Lazio, Italy, 00168
Legnago, Lombardia, Italy, 37045
Treviglio, Lombardia, Italy, 24047
S. Giovanni Rotondo, Puglia, Italy, 71013
Livorno, Toscana, Italy, 57124
Pisa, Toscana, Italy, 56100
Verona, Veneto, Italy, 37134
Korea, Republic of
Gyeonggi-do, Korea, Republic of, 463-707
Seoul, Korea, Republic of, 03722
Seoul, Korea, Republic of, 06351
Seoul, Korea, Republic of, 150-713
Suwon, Korea, Republic of, 442-723
Latvia
Daugavpils, Latvia, 5417
Riga, Latvia, LV-1079
Riga, Latvia, LV1002
Lithuania
Kaunas, Lithuania, 50009
Vilnius, Lithuania, 08660
Netherlands
Arnhem, Netherlands, 6800 TA
Heerlen, Netherlands, 6419 PC
Hoorn, Netherlands, 1625 HV
Sittard-Geleen, Netherlands, 6162 BG
Zutphen, Netherlands, 7207 AE
Poland
Brzozów, Poland, 36-200
Krakow, Poland, 31-115
Poznan, Poland, 60-569
Wodzislaw Slaski, Poland, 44-300
Zamosc, Poland, 22-400
Romania
Baia Mare, Romania, 430031
Braila, Romania, 810325
Brasov, Romania, 500091
Brasov, Romania, 500152
Bucuresti, Romania, 010976
Bucuresti, Romania, 022328
Cluj-Napoca, Romania, 400015
Cluj-Napoca, Romania, 400058
Cluj-Napoca, Romania, 400132
Oradea, Romania, 410167
Ploiesti, Romania, 100337
Targu-Mures, Romania, 540136
Slovakia
Banska Bystrica, Slovakia, 975 17
Bardejov, Slovakia, 085 01
Kosice, Slovakia, 04001
Nove Zamky, Slovakia, 940 02
Poprad, Slovakia, 058 01
Rimavska Sobota, Slovakia, 97901
South Africa
Cape Town, South Africa, 7570
Cape Town, South Africa, 7700
George, South Africa, 6530
Port Elizabeth, South Africa, 6045
Pretoria, South Africa, 0002
Taiwan
Kaohsiung, Taiwan, 00833
Taichung, Taiwan, 40447
Taichung, Taiwan, 40705
Taipei, Taiwan, 00112
Taipei, Taiwan, 100
Taipei, Taiwan, 112
Taipei, Taiwan, 11490
Thailand
Bangkok, Thailand, 10700
Hat Yai, Thailand, 90110
Muang, Thailand, 50200
Muang, Thailand, 57000
Ukraine
Dnipropetrovsk, Ukraine, 49102
Donetsk, Ukraine, 83092
Kharkiv, Ukraine, 61024
Kirovograd, Ukraine, 25011
Kyiv, Ukraine, 03022
Kyiv, Ukraine, 03115
Kyiv, Ukraine, 04107
Lutsk, Ukraine, 63000
Sumy, Ukraine, 40005
Uzhgorod, Ukraine, 88000
Vinnytsya, Ukraine, 21029
Zaporizhzhya, Ukraine, 69040
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01328951     History of Changes
Other Study ID Numbers: BO25460 
Study First Received: April 4, 2011
Results First Received: January 29, 2016
Last Updated: March 2, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Disease Progression
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Disease Attributes
Pathologic Processes
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2016