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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00858364
Recruitment Status : Terminated (Primary objective reached)
First Posted : March 9, 2009
Results First Posted : July 6, 2018
Last Update Posted : July 6, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE March 5, 2009
First Posted Date  ICMJE March 9, 2009
Results First Submitted Date  ICMJE June 7, 2018
Results First Posted Date  ICMJE July 6, 2018
Last Update Posted Date July 6, 2018
Actual Study Start Date  ICMJE July 17, 2009
Actual Primary Completion Date June 7, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 7, 2018)
Overall Survival (OS) [ Time Frame: From randomization until death or end of study; maximum time on follow-up was 93.6 months. ]
Overall survival (OS) was defined as the time from randomization to the date of death due to any cause. Participants were censored on the date of last contact (ie, the date the participant was last known to be alive) if they were not known to have died.
Original Primary Outcome Measures  ICMJE
 (submitted: March 5, 2009)
Overall Survival (OS) [ Time Frame: from randomization until death or end of study ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2018)
  • Progression-free Survival (PFS) [ Time Frame: From randomization until disease progression or death; maximum time on follow-up was 87.23 months. ]
    Progression-free survival was defined as the time from randomization to the date of radiographic disease progression or death from any cause, whichever event occurred first. Participants without either event were censored on the date of their last disease assessment. Disease progression was based on the investigator's assessment of scans using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 or 1.1 depending on the timing of enrollment.
  • Percentage of Participants With a Red Blood Cell Transfusion or Hemoglobin ≤ 8.0 g/dL From Week 5 to End of the Efficacy Treatment Period [ Time Frame: Week 5 (day 29) to end of the efficacy treatment period (EOETP; defined as 21 days after either the last dose of study drug or the last dose of chemotherapy, whichever was later); median (range) duration of dosing was 10 (1 to 106) weeks in both groups. ]
    Any red blood cell (RBC) transfusion (packed RBCs or whole blood) given or a hemoglobin ≤ 8.0 g/dL on or after study day 29 until the EOETP, inclusive.
  • Number of Participants With Adverse Events of Special Interest [ Time Frame: From first dose of study drug until 30 days after last dose; the median (range) duration of treatment was 10 (1 to 106) weeks in both groups. ]
    Adverse events of interest for darbepoetin alfa, based on clinical data in anemic patients with cancer to date, included the following categories: antibody-mediated pure red cell aplasia (PRCA), cardiac failure, central nervous system vascular disorders, convulsions, embolic and thrombotic events, hypersensitivity, hypertension, ischemic heart disease, malignancies, and severe cutaneous adverse reactions. Lack of efficacy and medication errors were also evaluated.
  • Percentage of Participants With an Objective Tumor Response [ Time Frame: Day 1 to end of the efficacy treatment period (EOETP; defined as 21 days after either the last dose of study drug or the last dose of chemotherapy, whichever was later); median (range) duration of dosing was 10 (1 to 106) weeks in both groups. ]
    Objective response was defined as the incidence of a complete or partial response at any time during the study. Response was determined by the investigator's assessment of the scans using RECIST version 1.0 or 1.1 depending on the timing of enrollment.
  • Number of Participants Who Developed Neutralizing Antibodies to Darbepoetin Alfa [ Time Frame: Baseline and end of the efficacy treatment period (EOETP; defined as 21 days after either the last dose of study drug or the last dose of chemotherapy, whichever was later. the median (range) duration of treatment was 10 (1 to 106) weeks in both groups. ]
    Developing antibody incidence was defined as neutralizing antibody positive postbaseline with a negative or no result at baseline.
  • Percentage of Participants With a Red Blood Cell Transfusion or Hemoglobin ≤ 8.0 g/dL From Week 1 to End of the Efficacy Treatment Period [ Time Frame: Week 1 to end of the efficacy treatment period (EOETP; defined as 21 days after either the last dose of study drug or the last dose of chemotherapy, whichever was later); the median (range) duration of treatment was 10 (1 to 106) weeks in both groups. ]
    Any red blood cell (RBC) transfusion (packed RBCs or whole blood) given or a hemoglobin ≤ 8.0 g/dL on or after study day 1 until the EOETP, inclusive.
  • Change From Baseline in Hemoglobin to End of Efficacy Treatment Period [ Time Frame: Baseline and end of the efficacy treatment period (EOETP; defined as 21 days after either the last dose of study drug or the last dose of chemotherapy, whichever was later); the median (range) duration of treatment was 10 (1 to 106) weeks in both groups. ]
    Post-baseline hemoglobin values within 28 days after a RBC transfusion were not be used in the calculation of change.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 5, 2009)
  • Objective tumor response [ Time Frame: randomization to subjects developing tumor progression ]
  • Incidence of neutralizing antibody formation to darbepoetin alfa [ Time Frame: first dose of investigative product to the end of treatment period ]
  • Incidence of at least 1 RBC transfusion or hemoglobin less than or equal to 8.0 g/dL from study day 1 to end of treatment period [ Time Frame: study day 1 until end of efficacy treatment period ]
  • Change in hemoglobin from baseline to end of efficacy treatment period [ Time Frame: screening until end of efficacy treatment period ]
  • Incidence of at least 1 RBC transfusion or hemoglobin less than or equal to 8.0 g/dL from week 5 (day 29) to end of efficacy treatment period [ Time Frame: Study day 29 to end of efficacy treatment period ]
  • Progression-free Survival (PFS) [ Time Frame: from randomization until disease progression ]
  • Incidence of adverse events (AEs) such as thrombovascular events (TVE), venous thromboembolic events (VTE), and AEs associated with RBC transfusions [ Time Frame: Randomization to 30 days after last dose of darbepoetin alfa ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Anemia Treatment for Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Receiving Chemotherapy
Official Title  ICMJE 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
Brief 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.
Detailed Description Oversight Authorities continued: Colombia
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Non-Small Cell Lung Cancer
  • Anemia
  • Cancer
  • Lung Cancer
Intervention  ICMJE
  • Drug: Darbepoetin alfa
    Administered subcutaneously once every 3 weeks
    Other Name: Aranesp®
  • Drug: Placebo
    Administered subcutaneously once every 3 weeks
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Participants received placebo once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.
    Intervention: Drug: Placebo
  • Experimental: Darbepoetin alfa
    Participants received darbepoetin alfa 500 µg once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.
    Intervention: Drug: Darbepoetin alfa
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 23, 2017)
2549
Original Estimated Enrollment  ICMJE
 (submitted: March 5, 2009)
3000
Actual Study Completion Date  ICMJE June 7, 2017
Actual Primary Completion Date June 7, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   Chile,   China,   Croatia,   Czechia,   Germany,   Greece,   Hong Kong,   India,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Luxembourg,   Malaysia,   Mexico,   Netherlands,   Philippines,   Poland,   Puerto Rico,   Romania,   Russian Federation,   Serbia,   Slovenia,   South Africa,   Spain,   Switzerland,   Taiwan,   Ukraine,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT00858364
Other Study ID Numbers  ICMJE 20070782
2007-005792-34 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Amgen
Study Sponsor  ICMJE Amgen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP