A Novel Erythropoiesis Stimulating Protein (NESP; Darbopoetin Alfa) for the Treatment of Anemia in Lung Cancer Patients Receiving Multi-cycle Platinum-Containing Chemotherapy

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

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.

Study Overview

• Status: Completed
• Conditions: Anemia
• Intervention / Treatment: Drug: Darbepoetin alfa; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 320
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Darbepoetin alfa; 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.	Drug: Darbepoetin alfa; Administered by subcutaneous injection once a week; Other Names: Aranesp; Novel Erythropoiesis Stimulating Protein (NESP)
Placebo Comparator: Placebo; Participants received once a week placebo, administered by subcutaneous injection for up to 12 weeks.	Drug: Placebo; Placebo matching to darbopoetin alfa administered by subcutaneous injection once a week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with a Red Blood Cell Transfusion During Weeks 5 to 12	Weeks 5 to 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 5 to week 12
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.	12 weeks
Time to Hemoglobin Response	The number of days from the first administration of study drug to the first occurrence of a hemoglobin response.	12 weeks
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.	12 weeks
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.	12 weeks
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.	12 weeks
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.	12 weeks
Time to Hemoglobin Correction	The number of days from the first administration of study drug to the first occurrence of a hemoglobin correction.	12 weeks
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.	12 weeks
Change from Baseline in Hemoglobin at Week 12		Baseline and week 12
Percentage of Participants who Received a Red Blood Cell Transfusion During Weeks 1 to 4, 5 to 8, and 9 to 12		Weeks 1 to 4, 5 to 8, and 9 to 12
Number of Standard Units of RBCs Transfused During Weeks 5 to 12		Weeks 5 to 12
Number of Days with RBC Transfusions During Weeks 5 to 12		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.	Baseline and week 12
Number of Participants with Adverse Events		16 weeks

Collaborators and Investigators

• Sponsor: Amgen

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 1999
• Primary Completion (Actual): November 8, 2000
• Study Completion (Actual): February 27, 2002

Study Registration Dates

• First Submitted: December 13, 2018
• First Submitted That Met QC Criteria: December 13, 2018
• First Posted (Actual): December 14, 2018

Study Record Updates

• Last Update Posted (Actual): December 20, 2018
• Last Update Submitted That Met QC Criteria: December 18, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Hematologic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Anemia; Hematinics; Darbepoetin alfa
• Other Study ID Numbers: 00980297

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No