Anemia Treatment for Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Receiving Chemotherapy

Oversight Authorities continued: Colombia

Inclusion Criteria:

- Subjects with stage IV NSCLC (not recurrent or re-staged).

- Expected to receive at least 2 additional cycles (at least 6 total weeks) of first
line myelosuppressive cyclic chemotherapy after randomization. Subjects should not be
expected to receive only maintenance chemotherapy.

- Eastern Cooperative Oncology Group performance status of 0 or 1 as assessed within 21
days prior to randomization.

- 18 years of age or older at screening.

- Life expectancy greater than 6 months based on the judgment of the investigator and
documented during screening.

- Hemoglobin level less than or equal to 11.0 g/dL as assessed by the local laboratory;
sample obtained within 7 days prior to randomization (retest in screening is
acceptable).

- Adequate serum folate (greater than or equal to 2 ng/mL) and vitamin B12 (greater than
or equal to 200 pg/mL) levels assessed by central laboratory (supplementation and
retest acceptable) during screening.

- Subjects must have had a baseline scan (computed tomography [CT], magnetic resonance
imaging [MRI], or positron emission tomography-computer tomography [PET/CT]) of the
chest to assess disease burden before starting on first line chemotherapy for NSCLC
and those images must have been reviewed by the investigator prior to randomization.
If the scan was performed more than 28 days prior to randomization, an additional scan
must be performed and reviewed by the investigator to confirm that the patient has not
progressed before randomization.

- Before any study-specific procedure, the appropriate written informed consent must be
obtained from the subject or a legally accepted representative.

Exclusion Criteria:

- Known primary benign or malignant hematologic disorder which can cause anemia.

- History of, or current active cancer other than NSCLC, with the exception of
curatively resected non-melanomatous skin cancer, curatively treated cervical
carcinoma in situ, or other primary solid tumors curatively treated with no known
active disease present and no curative treatment administered for the last 3 years.

- Received any prior adjuvant or neoadjuvant therapy for NSCLC.

- Subjects with a history of brain metastasis.

- Uncontrolled hypertension (systolic blood pressure [BP] > 160 mmHg or diastolic BP >
100 mmHg), or as determined by the investigator during screening.

- History of neutralizing antibody activity to recombinant human erythropoietin (rHuEPO)
or darbepoetin alfa.

- Uncontrolled angina, uncontrolled heart failure, or uncontrolled cardiac arrhythmia as
determined by the investigator at screening. Subjects with known myocardial infarction
within 6 months prior to randomization.

- Subjects with a history of seizure disorder taking anti-seizure medication within 30
days prior to randomization.

- Clinically significant systemic infection or uncontrolled chronic inflammatory disease
(eg, rheumatoid arthritis, inflammatory bowel disease) as determined by the
investigator during screening.

- Known seropositivity for human immunodeficiency virus (HIV) or diagnosis of acquired
immunodeficiency syndrome (AIDS), positive for hepatitis B surface antigen, or
seropositive for hepatitis C virus

- History of pure red cell aplasia

- History of deep venous thrombosis or embolic event (eg, pulmonary embolism) within 6
months prior to randomization.

- Transferrin saturation < 20% and ferritin < 50 ng/mL as assessed by the central
laboratory during screening. Subjects must have both to be excluded (supplementation
and retest acceptable).

- Abnormal renal function (serum creatinine level > 2X upper limit of normal [ULN]) as
assessed by the central laboratory during screening.

- Abnormal liver function (total bilirubin > 2X ULN or liver enzymes alanine
aminotransferase [ALT] or aspartate aminotransferase [AST] > 2.5X ULN for subjects
without liver metastasis or ≥ 5X ULN for subjects with liver metastasis) as assessed
by the central laboratory during screening. Subjects with documented Gilbert's Disease
may be eligible.

- Received any red blood cell (RBC) transfusion within 28 days prior to randomization.

- Plan to receive any RBC transfusion between randomization and study day 1.

- Known previous treatment failure to erythropoiesis stimulating agents (ESAs) (eg,
rHuEPO, darbepoetin alfa).

- ESA therapy within the 28 days prior to randomization.

- Known hypersensitivity to recombinant ESAs or the excipients contained within the
investigational product.

- Less than 30 days since receipt of any investigational product or device.
Investigational use/receipt of a medicinal product or device that has been approved by
the country's local regulatory authority for any indication is permitted.

- Subjects of reproductive potential who are pregnant, breast feeding or not willing to
use effective contraceptive precautions during the study and for at least one month
after the last dose of investigational product in the judgment of the investigator
(including females of childbearing potential who are partners of male subjects).

- Previously randomized to this study.

- Investigator has concerns regarding the ability of the subject to give written
informed consent and/or to comply with study procedures (including availability for
follow up visits).