Dose-finding Study of Novel Erythropoiesis Stimulating Protein (NESP) for the Treatment of Anaemia in Subjects With Solid Tumours Receiving Multicycle Chemotherapy

A Randomised, Double-blind, Placebo-controlled, Dose-finding Study of Novel Erythropoiesis Stimulating Protein (NESP) Administered by Subcutaneous (SC) Injection for the Treatment of Anaemia in Subjects With Solid Tumours Receiving Multicycle Chemotherapy

The purpose of this study is to assess the safety of NESP administered by SC injection in subjects with solid tumours and anaemia receiving multicycle chemotherapy.

Subjects in this study enter one of two schedules: Schedule 1 or Schedule 2. Schedule 1 is a sequential dose escalation study which consists of Parts A and B. Part A is the initial treatment phase, where the clinically effective dose (CED) of NESP administered every 3 weeks will be determined after 12 weeks of treatment. Part B is an optional 12-week, open-label, dose-maintenance phase that follows Part A.

Schedule 2 is a parallel dose-finding study and also consists of Parts A and B. Part A is the initial treatment phase, where the CED of NESP administered every 4 weeks will be determined after 12 weeks of treatment. Part B is an optional 12-week, open-label, dose-maintenance phase that follows Part A.

Study Overview

• Status: Completed
• Conditions: Anemia; Solid Tumors
• Intervention / Treatment: Drug: Placebo; Drug: Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa)

• Study Type: Interventional
• Enrollment (Anticipated): 405
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject with solid tumour(s)
• Anaemia (hgb less than or equal to 11.0 g/dL
• Planned to receive cyclic chemotherapy
• At least 6-month life expectancy
• Eastern Cooperative Oncology Group (ECOG) status of 0 to 2
• Adequate renal and liver function
• At least 18 years of age

Exclusion Criteria:

• Central nervous system disease
• Iron deficiency
• Received more than 2 RBC transfusions within 4 weeks before randomisation or any RBC transfusion within 2 weeks before randomisation
• Received recombinant human erythropoietin (rHuEPO) therapy within 8 weeks before randomisation
• History of any seizure disorder
• Cardiac disease
• Active infection or inflammatory disease
• Known positive test for HIV infection
• Known primary haematologic disorder which could cause anaemia
• Use of other investigational agent(s)/device(s)
• Pregnant or breast feeding
• Known hypersensitivity to any recombinant mammalian derived product

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NESP - Schedule 1 Part A; Part A - 4.5, 6.75, 9.0 or 13.5 mcg/kg Q3W for 12 weeks	Drug: Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa); Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa)
Experimental: NESP - Schedule 2 Part A; NESP 9.0, 12.0, 15.0 or 18.0 mcg/kg Q4W for 12 weeks	Drug: Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa); Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa)
Placebo Comparator: Placebo - Schedule 1 Part A; Placebo Q3W for 12 weeks	Drug: Placebo; Placebo
Experimental: NESP - Schedule 1 Part B; Open-label NESP at the dose of study drug administered at the end of Part A. Increase dose at week 19 if hgb < 13.0g/dL and/or RBC transfusion in previous 2 weeks.	Drug: Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa); Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa)
Placebo Comparator: Placebo - Schedule 2 Part A; Placebo Q4W for 12 weeks	Drug: Placebo; Placebo
Experimental: NESP - Schedule 2 Part B; Open-label NESP at the dose of study drug administered at the end of Part A	Drug: Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa); Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Occurence of adverse events and antibody formation to NESP	throughout the study

Secondary Outcome Measures

Outcome Measure	Time Frame
Number and proportion of subjects who receive any RBC transfusion, number of units of RBC transfused, and number of days with at least one RBC transfusion during weeks 1-12, 1-4, 5-8, 9-12, and 5-12, with emphasis on the 5-12 week window	during weeks 1-12, 1-4, 5-8, 9-12, and 5-12
Selected domains of quality of life (QOL) measured by FACT-G and FACT-anaemia scales, BSI depression and BSI anxiety scales, and de novo questions	throughout the study
Relationship between these QOL measurements and hgb
Hgb correction to greater than or equal to 12.0 g/dL in the absence of a red blood cell (RBC) transfusion during the preceding 4 weeks during treatment phase	during treatment phase
Number and proportion of subjects, during the treatment phase, who achieve a hemoglobin (hgb) response	during the treatment phase
Time to hgb response and hgb correction after the initiation of treatment	after the initiation of treatment
Change in hgb measured at the end of the treatment phase compared to baseline	baseline to end of the treatment phase

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Kotasek D, Steger G, Faught W, Underhill C, Poulsen E, Colowick AB, Rossi G, Mackey J; Aranesp 980291 Study Group. Darbepoetin alfa administered every 3 weeks alleviates anaemia in patients with solid tumours receiving chemotherapy; results of a double-blind, placebo-controlled, randomised study. Eur J Cancer. 2003 Sep;39(14):2026-34. doi: 10.1016/s0959-8049(03)00456-8.

Helpful Links

• AmgenTrials clinical trials website
• Notice regarding posted summaries of trial results
• FDA-approved Drug Labeling
• To access clinical trial results information click on this link

Study record dates

Study Major Dates

• Study Start: July 1, 1999
• Primary Completion (Actual): March 1, 2002
• Study Completion (Actual): June 1, 2002

Study Registration Dates

• First Submitted: October 4, 2007
• First Submitted That Met QC Criteria: October 4, 2007
• First Posted (Estimate): October 8, 2007

Study Record Updates

• Last Update Posted (Estimate): May 8, 2013
• Last Update Submitted That Met QC Criteria: May 6, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Solid tumors; Anemia; NESP; Multicycle chemotherapy
• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia; Hematinics; Darbepoetin alfa
• Other Study ID Numbers: 980291