Erlotinib Hydrochloride in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Completely Removed by Surgery (An ALCHEMIST Treatment Trial)
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| ClinicalTrials.gov Identifier: NCT02193282 |
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Recruitment Status :
Recruiting
First Posted : July 17, 2014
Last Update Posted : February 20, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| ALK Gene Rearrangement EGFR Exon 19 Deletion Mutation EGFR NP_005219.2:p.L858R Stage IB Non-Small Cell Lung Carcinoma AJCC v7 Stage II Non-Small Cell Lung Cancer AJCC v7 Stage IIA Non-Small Cell Lung Carcinoma AJCC v7 Stage IIB Non-Small Cell Lung Carcinoma AJCC v7 Stage IIIA Non-Small Cell Lung Cancer AJCC v7 | Other: Clinical Observation Drug: Erlotinib Hydrochloride Other: Laboratory Biomarker Analysis Other: Placebo | Phase 3 |
PRIMARY OBJECTIVES:
I. To assess whether adjuvant therapy with erlotinib (erlotinib hydrochloride) will result in improved overall survival (OS) over observation for patients with completely resected stage IB (>= 4 cm)-IIIA epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) (confirmed centrally) following complete resection and standard post-operative therapy.
SECONDARY OBJECTIVES:
I. To assess whether adjuvant therapy with erlotinib will result in improved disease free survival (DFS) over observation for patients with completely resected stage IB (>= 4 cm)-IIIA EGFR mutant NSCLC (confirmed centrally) following complete resection and standard post-operative therapy, both overall and within the stage subgroups: IB and II/IIIA.
II. To evaluate the safety profile of erlotinib in the adjuvant setting. III. To assess whether adjuvant therapy with erlotinib will result in improved DFS rate at 2 years, and OS rate at 5 and 10 years over observation for patients with completely resected stage IB (>= 4 cm)-IIIA EGFR mutant NSCLC (confirmed centrally) following complete resection and standard post-operative therapy, both overall and within the stage subgroups: IB and II/IIIA.
IV. To assess the primary and secondary objectives in all randomized patients, regardless of central confirmation of the EGFR mutant status.
V. To study detection of circulating EGFR mutations in cell-free plasma deoxyribonucleic acid (DNA) as a prognostic marker in resected early stage NSCLC.
OUTLINE: Patients are randomized to 1 of 4 treatment arms.
ARM A (BLINDED ERLOTINIB- CLOSED 06/14/17): Blinded patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
ARM B (PLACEBO- CLOSED 06/14/17): Patients receive placebo PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
ARM C (UNBLINDED ERLOTINIB): Unblinded patients receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
ARM D (OBSERVATION): Patients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years.
After completion of study treatment, patients are followed up every 6 months for 4 years and then yearly for 6 years.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 450 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Masking Description: | As of June 15, 2017, sites will sign into RAVE to unblind any patients that had previously enrolled |
| Primary Purpose: | Treatment |
| Official Title: | Randomized Study of Erlotinib vs Observation in Patients With Completely Resected Epidermal Growth Factor Receptor (EGFR) Mutant Non-Small Cell Lung Cancer (NSCLC) |
| Actual Study Start Date : | August 18, 2014 |
| Estimated Primary Completion Date : | November 4, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm A (blinded erlotinib hydrochloride)
Blinded patients receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. (CLOSED 06/14/17)
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Drug: Erlotinib Hydrochloride
Given PO
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies |
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Placebo Comparator: Arm B (placebo)
Patients receive placebo PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. (CLOSED 06/14/17)
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Other: Laboratory Biomarker Analysis
Correlative studies Other: Placebo Given PO
Other Names:
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Experimental: Arm C (unblinded erlotinib hydrochloride)
Unblinded patients receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
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Drug: Erlotinib Hydrochloride
Given PO
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies |
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Active Comparator: Arm D (observation)
Patients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years.
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Other: Clinical Observation
Undergo observation
Other Name: observation Other: Laboratory Biomarker Analysis Correlative studies |
- Overall survival (OS) [ Time Frame: The time from randomization until death, assessed up to 10 years ]Estimated using the method of Kaplan-Meier survival curves and a 1-sided stratified log rank test (accounting for all the stratification factors) will be used to compare OS between the two arms. Cox proportional hazards model (including time varying coefficients as necessary) will be used to assess whether the distribution of OS times differ with respect to treatment regimen after having adjusted for the stratification factors as well as other potential prognostic and treatment covariates.
- Disease free survival (DFS) rate [ Time Frame: Time from randomization until documented disease-recurrence or death, whichever occurs first, assessed at 2 years ]DFS will be defined as the proportion of patients alive and disease free at 2 years from the date of randomization. Estimated using the method of Kaplan-Meier survival curves. A 1-sided stratified log rank test (accounting for all the stratification factors) will be used to compare DFS between the arms, as well as to compare DFS and OS between the arms within the stage groups. Cox proportional hazards model (including time varying coefficients as necessary) will be used to assess potential differences in time to event outcomes after adjusting for the stratification factors and other potential prognostic and treatment covariates.
- Overall survival (OS) rate at 5 years [ Time Frame: At 5 years ]Will be defined as the proportion of patients alive at 5 years from date of randomization. Estimated using the method of Kaplan-Meier survival curves. A 1-sided stratified log rank test (accounting for all the stratification factors) will be used to compare DFS between the arms, as well as to compare DFS and OS between the arms within the stage groups. Cox proportional hazards model (including time varying coefficients as necessary) will be used to assess potential differences in time to event outcomes after adjusting for the stratification factors and other potential prognostic and treatment covariates.
- Overall survival (OS) rate at 10 years [ Time Frame: At 10 years ]Will be defined as the proportion of patients alive at 10 years from date of randomization. Estimated using the method of Kaplan-Meier survival curves. A 1-sided stratified log rank test [accounting for all the stratification factors] will be used to compare DFS and OS between the arms within the stage groups. Cox proportional hazards model (including time varying coefficients as necessary) will be used to assess potential differences in time to event outcomes after adjusting for the stratification factors and other potential prognostic and treatment covariates.
- Overall disease free survival (DFS) between the erlotinib hydrochloride and observation arms [ Time Frame: Time from randomization until documented disease-recurrence or death, whichever occurs first, assessed up to 10 years ]Estimated using the method of Kaplan-Meier survival curves (21). A 1-sided stratified log rank test [accounting for all the stratification factors] will be used to compare DFS between the arms, as well as to compare DFS and OS between the arms within the stage groups. Cox proportional hazards model (including time varying coefficients as necessary) will be used to assess potential differences in time to event outcomes after adjusting for the stratification factors and other potential prognostic and treatment covariates.
- Incidence of adverse events associated with each treatment arm [ Time Frame: Up to 10 years ]The maximum grade for each type of adverse event will be recorded for each patient and frequency tables will be reviewed to determine the overall patterns. The number and severity of grade 3 + adverse events will be tabulated and summarized. All adverse events analysis will entail comparisons between the arms within Arms A and B, respectively. Analysis of the overall adverse event rates, as well as specific events of interest will involve chi-square tests or Fisher's exact tests.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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Previously registered to A151216, with the result of lung cancer harboring an EGFR exon 19 deletion or L858R mutation; the testing must have been performed by one of the following criteria:
- Patient registered to A151216 and the assessment performed centrally by the protocol-specified laboratory
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By a local Clinical Laboratory Improvement Amendments (CLIA) certified laboratory; the report must indicate the result as well as the CLIA number of the laboratory that performed the assay; these patients will also have been registered to A151216, but can be enrolled on A081105 regardless of the central lab results
- Patients with known resistant mutations in the EGFR tyrosine-kinase (TK) domain (T790M) are not eligible
- Patients that are both EGFR mutant and anaplastic lymphoma kinase (ALK) rearrangements will be registered to A081105
- Completely resected stage IB (>= 4 cm), II or IIIA non-squamous NSCLC with negative margins; patients may not have received neoadjuvant therapy (chemo- or radio-therapy) for this lung cancer
- Complete recovery from surgery and standard post-operative therapy (if required); patients must be completely recovered from surgery at the time of randomization; the minimum time requirement between date of surgery and randomization must be at least 28 days, the maximum time requirement between surgery and randomization must be 90 days if no adjuvant chemotherapy was administered, 240 days if adjuvant chemotherapy was administered, and 300 days if adjuvant chemotherapy and radiation therapy was administered
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- No locally advanced or metastatic cancer requiring systemic therapy within 5 years prior to registration; no secondary primary lung cancer diagnosed concurrently or within 2 years prior to registration
- Non-pregnant and non-lactating
- No history of cornea abnormalities
- Granulocytes >= 1,500/ul
- Platelets >= 100,000/ul
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Serum glutamic oxaloacetic transaminase (SGOT) =< 1.5 x ULN
- Serum creatinine =< 1.5 x ULN
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02193282
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| Principal Investigator: | Ramaswamy Govindan | Alliance for Clinical Trials in Oncology |
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT02193282 History of Changes |
| Other Study ID Numbers: |
NCI-2014-01508 NCI-2014-01508 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) s16-02079 CALGB A081105 A081105 ( Other Identifier: Alliance for Clinical Trials in Oncology ) A081105 ( Other Identifier: CTEP ) U10CA180821 ( U.S. NIH Grant/Contract ) U10CA180830 ( U.S. NIH Grant/Contract ) U10CA031946 ( U.S. NIH Grant/Contract ) |
| First Posted: | July 17, 2014 Key Record Dates |
| Last Update Posted: | February 20, 2019 |
| Last Verified: | February 2019 |
Additional relevant MeSH terms:
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Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site |
Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Erlotinib Hydrochloride Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |