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

April 4, 2011
March 2, 2016
September 2011
December 2015   (final data collection date for primary outcome measure)
  • 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.
Overall survival (OS): First-line maintenance Tarceva versus Tarceva at time of disease progression [ Time Frame: 42 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01328951 on ClinicalTrials.gov Archive Site
  • 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.
  • Progression-free survival (PFS): First-line maintenance Tarceva versus placebo (tumour assessments according to RECIST criteria) [ Time Frame: 42 months ] [ Designated as safety issue: No ]
  • Overall response rate (ORR): First-line maintenance Tarceva versus placebo [ Time Frame: 42 months ] [ Designated as safety issue: No ]
  • Disease control rate (DCR): First-line maintenance Tarceva versus placebo [ Time Frame: 42 months ] [ Designated as safety issue: No ]
  • Safety: Incidence of adverse events [ Time Frame: 42 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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
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
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.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Non-Squamous Non-Small Cell Lung Cancer
  • 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
  • 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.
  • 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.
    Interventions:
    • Drug: Erlotinib
    • Drug: Second-Line Chemotherapy
  • 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.
    Interventions:
    • Drug: Placebo
    • Drug: Erlotinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
643
January 2016
December 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Brazil,   Bulgaria,   Canada,   China,   Czech Republic,   France,   Hungary,   Italy,   Korea, Republic of,   Latvia,   Lithuania,   Netherlands,   Poland,   Romania,   Slovakia,   South Africa,   Taiwan,   Thailand,   Ukraine
Germany
 
NCT01328951
BO25460
Not Provided
Not Provided
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP