A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Long-term Safety and Efficacy of Darbepoetin Alfa Administered at 500 µg Once-Every-3-Weeks in Anemic Subjects With Advanced Stage Non-small Cell Lung Cancer Receiving Multi-cycle Chemotherapy
- 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
- 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 (CT, MRI, or 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.
- 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 BP > 160 mmHg or diastolic BP > 100 mmHg), or as
determined by the investigator during screening.
- History of neutralizing antibody activity to 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 HIV or diagnosis of 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 ULN) as assessed by the central
laboratory during screening.
- Abnormal liver function (total bilirubin > 2X ULN or liver enzymes ALT or 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 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 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
- 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).