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)

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.

Inclusion Criteria:

- 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:

1. Patient registered to A151216 and the assessment performed centrally by the
protocol-specified laboratory

2. 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