A Novel Erythropoiesis Stimulating Protein (NESP; Darbopoetin Alfa) for the Treatment of Anemia in Lung Cancer Patients Receiving Multi-cycle Platinum-Containing Chemotherapy
Primary Purpose
Anemia
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Darbepoetin alfa
Placebo
Sponsored by

About this trial
This is an interventional treatment trial for Anemia focused on measuring Lung cancer
Eligibility Criteria
Inclusion Criteria:
- Lung cancer (either small cell [SCLC] or non-small cell [NSCLC])
- At least 12 additional weeks of platinum containing cyclic chemotherapy planned regardless of cycle length
- Anemia (hemoglobin ≤ 11.0 g/dL) as assessed by a local or central laboratory result within 7 days before study day 1 (the first scheduled day of on-study chemotherapy and the first day of study drug administration)
- Life expectancy of at least 6 months, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
- Anemia predominantly due to the cancer or chemotherapy (i.e.. serum folate ≥ 4.5 nmol/L (≥ 2.0 ng/mL) and vitamin B 12 ≥ 148 pmol/L (≥ 200 pg/mL), no overt hemolysis, and no overt gastrointestinal bleeding or bleeding due to recent surgery)
- Adequate renal function (creatinine ≤ 177gmol/L (≤ 2.0 mg/dL) and adequate hepatic function (bilirubin ≤ 1.5 times central laboratory's upper limit of normal range)
- Available for 4 weeks post administration of the last dose of study drug
- Legal age for informed consent, and written informed consent must be obtained
Exclusion Criteria:
- History of any primary hematological disorder which could cause anemia (e.g., sickle cell anemia)
- Received prior whole pelvis radiation therapy
- Uncontrolled angina, congestive heart failure (New York Heart Association > class II or known ejection fraction < 40%)], or uncontrolled cardiac arrhythmia.
- History of primary or metastatic malignancy involving the central nervous system (CNS). Subjects with a previous history of primary or metastatic malignancy involving the CNS will be eligible for the study providing they have had no clinical signs of nor treatment for CNS disease and no history of seizures within previous 2 years
- Uncontrolled hypertension (i.e., diastolic blood pressure > 100 mm Hg)
- History of seizures. Subjects with a previous history of seizures will be eligible for the study providing they have had no evidence of seizure activity and have been free of anti-seizure medication for the previous 5 years
- Evidence of clinically significant systemic active infection or chronic inflammatory disease (e.g., rheumatoid arthritis)
- Iron deficiency (transferrin saturation < 15% and ferritin < 10 μg/L (< 10 ng/mL))
- Received > 2 RBC transfusions within 4 weeks before randomization or any RBC transfusion within 2 weeks before randomization
- Received erythropoietin therapy within 8 weeks before randomization
- Known positive test for human immunodeficiency virus (HIV) infection
- Receiving, or not yet 30 days past the end of receiving, another investigational agent or device not approved in any indication.
- Pregnant or breast feeding females.
- Not using adequate contraceptive precautions
- Prior treatment with NESP
- Previously randomized in this study
- Known hypersensitivity to mammalian-derived product
- Concerns for subject's compliance with the protocol procedure, including completion of the quality of life surveys (QOLS)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Darbepoetin alfa
Placebo
Arm Description
Participants received once a week darbepoetin alfa, administered by subcutaneous injection at a starting dose of 2.25 µg/kg for up to 12 weeks. The dose of darbepoetin alfa may have been adjusted based on hemoglobin levels to a maximum dose of 4.5 µg/kg /week.
Participants received once a week placebo, administered by subcutaneous injection for up to 12 weeks.
Outcomes
Primary Outcome Measures
Percentage of Participants with a Red Blood Cell Transfusion During Weeks 5 to 12
Secondary Outcome Measures
Time to First Red Blood Cell Transfusion During Weeks 5 to 12
The number of days from the first day of study week 5 (day 29) to the first administration of a RBC transfusion during the Treatment Phase that occurs on or after day 29.
Percentage of Participants with a Hemoglobin Response by Week 12
Hemoglobin Response was defined as an increase in hemoglobin of ≥ 2.0 g/dL over baseline hemoglobin in the absence of any RBC transfusions during the preceding 28 days.
Time to Hemoglobin Response
The number of days from the first administration of study drug to the first occurrence of a hemoglobin response.
Percentage of Participants who Achieved a Sustained Hemoglobin Response by Week 12
Sustained hemoglobin response was defined as in increase in hemoglobin of ≥ 2.0 g/dL over baseline hemoglobin sustained for at least 28 days or until the end of the Treatment Phase. This increase must have occurred in the absence of RBC transfusions during the period of sustained response and the preceding 28 days.
Time to Sustained Hemoglobin Response
The number of days from the first administration of study drug to the first occurrence of a sustained hemoglobin response.
Percentage of Participants who Achieved a Hemoglobin Correction by Week 12
Hemoglobin correction was defined as a hemoglobin value of ≥ 12.0 g/dL that occurred in the absence of RBC transfusions during the preceding 28 days.
Percentage of Participants who Achieved a Sustained Hemoglobin Correction by Week 12
Sustained hemoglobin correction was defined as a hemoglobin value of ≥ 12.0 g/dL that was sustained for at least 28 days or until the end of the Treatment Phase. This must have occurred in the absence of RBC transfusions during the period of sustained correction and the preceding 28 days.
Time to Hemoglobin Correction
The number of days from the first administration of study drug to the first occurrence of a hemoglobin correction.
Time to Sustained Hemoglobin Correction
The number of days from the first administration of study drug to the first occurrence of a sustained hemoglobin correction.
Change from Baseline in Hemoglobin at Week 12
Percentage of Participants who Received a Red Blood Cell Transfusion During Weeks 1 to 4, 5 to 8, and 9 to 12
Number of Standard Units of RBCs Transfused During Weeks 5 to 12
Number of Days with RBC Transfusions During Weeks 5 to 12
Change from Baseline in the Functional Assessment of Cancer Therapy (FACT)-Anemia Subscales at Week 12
The FACT-anemia is a 47-item questionnaire to assess specific quality of life concerns related to anemia and fatigue in cancer patients.
Number of Participants with Adverse Events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03776032
Brief Title
A Novel Erythropoiesis Stimulating Protein (NESP; Darbopoetin Alfa) for the Treatment of Anemia in Lung Cancer Patients Receiving Multi-cycle Platinum-Containing Chemotherapy
Official Title
A Double-Blind, Placebo Controlled, Randomised Study of Novel Erythropoiesis Stimulating Protein (NESP) for the Treatment of Anaemia in Lung Cancer Subjects Receiving Multicycle Platinum-Containing Chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
September 14, 1999 (Actual)
Primary Completion Date
November 8, 2000 (Actual)
Study Completion Date
February 27, 2002 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective of this study was to compare the effectiveness of darbopoetin alfa to placebo in the treatment of anemia in adults with lung cancer receiving multicycle platinum-containing chemotherapy, by assessing the percentage of participants who received red blood cell (RBC) transfusions during weeks 5-12 inclusive.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia
Keywords
Lung cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
320 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Darbepoetin alfa
Arm Type
Experimental
Arm Description
Participants received once a week darbepoetin alfa, administered by subcutaneous injection at a starting dose of 2.25 µg/kg for up to 12 weeks. The dose of darbepoetin alfa may have been adjusted based on hemoglobin levels to a maximum dose of 4.5 µg/kg /week.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received once a week placebo, administered by subcutaneous injection for up to 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Darbepoetin alfa
Other Intervention Name(s)
Novel Erythropoiesis Stimulating Protein (NESP), Aranesp
Intervention Description
Administered by subcutaneous injection once a week
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo matching to darbopoetin alfa administered by subcutaneous injection once a week.
Primary Outcome Measure Information:
Title
Percentage of Participants with a Red Blood Cell Transfusion During Weeks 5 to 12
Time Frame
Weeks 5 to 12
Secondary Outcome Measure Information:
Title
Time to First Red Blood Cell Transfusion During Weeks 5 to 12
Description
The number of days from the first day of study week 5 (day 29) to the first administration of a RBC transfusion during the Treatment Phase that occurs on or after day 29.
Time Frame
Week 5 to week 12
Title
Percentage of Participants with a Hemoglobin Response by Week 12
Description
Hemoglobin Response was defined as an increase in hemoglobin of ≥ 2.0 g/dL over baseline hemoglobin in the absence of any RBC transfusions during the preceding 28 days.
Time Frame
12 weeks
Title
Time to Hemoglobin Response
Description
The number of days from the first administration of study drug to the first occurrence of a hemoglobin response.
Time Frame
12 weeks
Title
Percentage of Participants who Achieved a Sustained Hemoglobin Response by Week 12
Description
Sustained hemoglobin response was defined as in increase in hemoglobin of ≥ 2.0 g/dL over baseline hemoglobin sustained for at least 28 days or until the end of the Treatment Phase. This increase must have occurred in the absence of RBC transfusions during the period of sustained response and the preceding 28 days.
Time Frame
12 weeks
Title
Time to Sustained Hemoglobin Response
Description
The number of days from the first administration of study drug to the first occurrence of a sustained hemoglobin response.
Time Frame
12 weeks
Title
Percentage of Participants who Achieved a Hemoglobin Correction by Week 12
Description
Hemoglobin correction was defined as a hemoglobin value of ≥ 12.0 g/dL that occurred in the absence of RBC transfusions during the preceding 28 days.
Time Frame
12 weeks
Title
Percentage of Participants who Achieved a Sustained Hemoglobin Correction by Week 12
Description
Sustained hemoglobin correction was defined as a hemoglobin value of ≥ 12.0 g/dL that was sustained for at least 28 days or until the end of the Treatment Phase. This must have occurred in the absence of RBC transfusions during the period of sustained correction and the preceding 28 days.
Time Frame
12 weeks
Title
Time to Hemoglobin Correction
Description
The number of days from the first administration of study drug to the first occurrence of a hemoglobin correction.
Time Frame
12 weeks
Title
Time to Sustained Hemoglobin Correction
Description
The number of days from the first administration of study drug to the first occurrence of a sustained hemoglobin correction.
Time Frame
12 weeks
Title
Change from Baseline in Hemoglobin at Week 12
Time Frame
Baseline and week 12
Title
Percentage of Participants who Received a Red Blood Cell Transfusion During Weeks 1 to 4, 5 to 8, and 9 to 12
Time Frame
Weeks 1 to 4, 5 to 8, and 9 to 12
Title
Number of Standard Units of RBCs Transfused During Weeks 5 to 12
Time Frame
Weeks 5 to 12
Title
Number of Days with RBC Transfusions During Weeks 5 to 12
Time Frame
Weeks 5 to 12
Title
Change from Baseline in the Functional Assessment of Cancer Therapy (FACT)-Anemia Subscales at Week 12
Description
The FACT-anemia is a 47-item questionnaire to assess specific quality of life concerns related to anemia and fatigue in cancer patients.
Time Frame
Baseline and week 12
Title
Number of Participants with Adverse Events
Time Frame
16 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Lung cancer (either small cell [SCLC] or non-small cell [NSCLC])
At least 12 additional weeks of platinum containing cyclic chemotherapy planned regardless of cycle length
Anemia (hemoglobin ≤ 11.0 g/dL) as assessed by a local or central laboratory result within 7 days before study day 1 (the first scheduled day of on-study chemotherapy and the first day of study drug administration)
Life expectancy of at least 6 months, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Anemia predominantly due to the cancer or chemotherapy (i.e.. serum folate ≥ 4.5 nmol/L (≥ 2.0 ng/mL) and vitamin B 12 ≥ 148 pmol/L (≥ 200 pg/mL), no overt hemolysis, and no overt gastrointestinal bleeding or bleeding due to recent surgery)
Adequate renal function (creatinine ≤ 177gmol/L (≤ 2.0 mg/dL) and adequate hepatic function (bilirubin ≤ 1.5 times central laboratory's upper limit of normal range)
Available for 4 weeks post administration of the last dose of study drug
Legal age for informed consent, and written informed consent must be obtained
Exclusion Criteria:
History of any primary hematological disorder which could cause anemia (e.g., sickle cell anemia)
Received prior whole pelvis radiation therapy
Uncontrolled angina, congestive heart failure (New York Heart Association > class II or known ejection fraction < 40%)], or uncontrolled cardiac arrhythmia.
History of primary or metastatic malignancy involving the central nervous system (CNS). Subjects with a previous history of primary or metastatic malignancy involving the CNS will be eligible for the study providing they have had no clinical signs of nor treatment for CNS disease and no history of seizures within previous 2 years
Uncontrolled hypertension (i.e., diastolic blood pressure > 100 mm Hg)
History of seizures. Subjects with a previous history of seizures will be eligible for the study providing they have had no evidence of seizure activity and have been free of anti-seizure medication for the previous 5 years
Evidence of clinically significant systemic active infection or chronic inflammatory disease (e.g., rheumatoid arthritis)
Iron deficiency (transferrin saturation < 15% and ferritin < 10 μg/L (< 10 ng/mL))
Received > 2 RBC transfusions within 4 weeks before randomization or any RBC transfusion within 2 weeks before randomization
Received erythropoietin therapy within 8 weeks before randomization
Known positive test for human immunodeficiency virus (HIV) infection
Receiving, or not yet 30 days past the end of receiving, another investigational agent or device not approved in any indication.
Pregnant or breast feeding females.
Not using adequate contraceptive precautions
Prior treatment with NESP
Previously randomized in this study
Known hypersensitivity to mammalian-derived product
Concerns for subject's compliance with the protocol procedure, including completion of the quality of life surveys (QOLS)
12. IPD Sharing Statement
Learn more about this trial
A Novel Erythropoiesis Stimulating Protein (NESP; Darbopoetin Alfa) for the Treatment of Anemia in Lung Cancer Patients Receiving Multi-cycle Platinum-Containing Chemotherapy
We'll reach out to this number within 24 hrs