Anemia Treatment for Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Receiving Chemotherapy
Condition: Non-Small Cell Lung Cancer; Anemia; Cancer; Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Anemia
Intervention: Darbepoetin alfa; Placebo
Intervention description: Administered subcutaneously once every 3 weeks; Administered subcutaneously once every 3 weeks
Intervention MeSH terms: Darbepoetin alfa
Phase: Phase 3
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 2549.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: darbepoetin alfa; non-small cell lung cancer; Aranesp; chemotherapy; chemotherapy induce anemia; advanced lung cancer; malignant pleural effusion; metastatic lung cancer; NSCLC; anemia; lung cancer; pleural effusion; Stage IIIB lung cancer; Stage IV lung cancer

Summary:

      This is a study in patients with chemotherapy induced anemia receiving multi-cycle
      chemotherapy for the treatment of stage IV non-small cell lung cancer (NSCLC). The primary
      objective of the study is to demonstrate that overall survival (OS) is not worse in
      participants on darbepoetin alfa treated to a hemoglobin ceiling of 12.0 g/dL compared to
      participants treated with placebo.
    

Eligibility criteria:

        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).