Effect of Darbepoetin Alfa (Aranesp®) on Anemia in Patients With Advanced Hormone Independent Prostate Cancer
NCT ID: NCT00381836
Last Updated: 2015-12-04
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
TERMINATED
Clinical Phase
PHASE2/PHASE3
Total Enrollment
140 participants
Study Classification
INTERVENTIONAL
Study Start Date
2006-10-31
Study Completion Date
2007-02-28
Brief Summary
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The purpose of this study is to determine whether or not Aranesp® (Darbepoetin Alfa), administered every fourth week, is effective in the treatment of blood shortage (anemia) compared to standard care of treatment (blood transfusions) in patients with anemia due to hormone refractory prostate cancer.
Detailed Description
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In the past, prostate cancer has been regarded a relatively benign disease, which elderly men were expected to die with rather than from, however, prostate cancer has become the second most common non-skin cancer in Danish men and the second most common cause of male cancer death. Two out of three patients with clinically significant prostate cancer die from and not with their cancer disease, and the misery of this population is evident. Regular treatments with opiates or equivalent drugs as well are required in nearly one third of the patients.
Patients with advanced hormone insensitive (refractory) prostate cancer have a median survival rate of about one year and during this time they often suffer from anemia due to reasons like blood loss, tumor infiltration of the bone marrow and even treatment with androgen deprivation. Compared to patients with other cancer types patients with prostate cancer have a significantly lower mean haemoglobin level. However, patients with hormone refractory prostate cancer have not previously been given much attention and the treatment of the frequent condition of chronic anemia in this group of patients seems casual. Therefore, Best Standard of Care (BSC) is defined as RBC transfusion if the hemoglobin is \< 5,0 mmol/L (8,0 g/dl), and if there are signs or symptoms of anemia and supplemental iron if se-ferritin \< 200 mcg/L.
Very little is known about erythropoietin treatment and quality of life in hormone refractory prostate cancer patients. A randomized Swedish study did investigate the influence of two different doses of epoetin beta on quality of life, hemoglobin level, need for red blood cell transfusion and safety, in the treatment of anemia in 180 patients suffering from advanced hormone-refractory prostate cancer. This study found the treatment to be safe and effective for the treatment in many of these patients. In many of these critically ill patients, the treatment improved quality of life and relieved fatigue symptoms.
Darbepoetin alpha (Aranesp®) is produced by gene-technology in Chinese Hamster Cells (CHO-K1). It has a biological effect and toxicity profile comparable to r-HuEPO; with the exception of a longer half-life which means that it can be administered less frequently without loosing clinical efficiency. Aranesp® has been well tolerated in studies conducted to this date. In this setting Aranesp® appears to be safe and well tolerated. Adverse events reported to date have generally been mild to moderate in severity and consistent with events and symptoms in cancer patients with chronic disease receiving chemotherapy (i.e. fatigue and gastrointestinal symptoms). Clinical studies have shown a higher frequency of thromboembolic reactions including deep vein thrombosis and pulmonary embolism in cancer patients receiving Aranesp therapy compared to patients receiving placebo. The clinical experience so far with Aranesp® has been published (15,16,17). Aranesp® is registered for clinical use in Europe and US.
Based on this the present study will evaluate the effect of Aranesp® on the haematopoietic response in patients with advanced hormone independent prostate cancer and anemia. Moreover, the effect of Aranesp® on quality of life, hemoglobin, necessity for RBC transfusion and hospital admissions, will be evaluated. The study will be performed as an open randomized trial. The use of r-HuEPO in cancer patients has been established and registered in other settings (as supportive treatment), and it has been shown that the preparation can be given without significant side effects. On the contrary, it is likely that patients may benefit from additional improvement in wellbeing.
Patients with advanced hormone insensitive (refractory) prostate cancer have a median survival rate of about one year and during this time they often suffer from anemia due to reasons like blood loss, tumor infiltration of the bone marrow and even treatment with androgen deprivation. Compared to patients with other cancer types patients with prostate cancer have a significantly lower mean haemoglobin level. However, patients with hormone refractory prostate cancer have not previously been given much attention and the treatment of the frequent condition of chronic anemia in this group of patients seems casual. Therefore, Best Standard of Care (BSC) is defined as RBC transfusion if the hemoglobin is \< 5,0 mmol/L (8,0 g/dl), and if there are signs or symptoms of anemia and supplemental iron if se-ferritin \< 200 mcg/L.
Very little is known about erythropoietin treatment and quality of life in hormone refractory prostate cancer patients. A randomized Swedish study did investigate the influence of two different doses of epoetin beta on quality of life, hemoglobin level, need for red blood cell transfusion and safety, in the treatment of anemia in 180 patients suffering from advanced hormone-refractory prostate cancer. This study found the treatment to be safe and effective for the treatment in many of these patients. In many of these critically ill patients, the treatment improved quality of life and relieved fatigue symptoms.
Darbepoetin alpha (Aranesp®) is produced by gene-technology in Chinese Hamster Cells (CHO-K1). It has a biological effect and toxicity profile comparable to r-HuEPO; with the exception of a longer half-life which means that it can be administered less frequently without loosing clinical efficiency. Aranesp® has been well tolerated in studies conducted to this date. In this setting Aranesp® appears to be safe and well tolerated. Adverse events reported to date have generally been mild to moderate in severity and consistent with events and symptoms in cancer patients with chronic disease receiving chemotherapy (i.e. fatigue and gastrointestinal symptoms). Clinical studies have shown a higher frequency of thromboembolic reactions including deep vein thrombosis and pulmonary embolism in cancer patients receiving Aranesp therapy compared to patients receiving placebo. The clinical experience so far with Aranesp® has been published (15,16,17). Aranesp® is registered for clinical use in Europe and US.
Based on this the present study will evaluate the effect of Aranesp® on the haematopoietic response in patients with advanced hormone independent prostate cancer and anemia. Moreover, the effect of Aranesp® on quality of life, hemoglobin, necessity for RBC transfusion and hospital admissions, will be evaluated. The study will be performed as an open randomized trial. The use of r-HuEPO in cancer patients has been established and registered in other settings (as supportive treatment), and it has been shown that the preparation can be given without significant side effects. On the contrary, it is likely that patients may benefit from additional improvement in wellbeing.
Conditions
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Prostatic Neoplasms
Anemia
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Primary Study Purpose
SUPPORTIVE_CARE
Blinding Strategy
NONE
Interventions
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Darbepoetin Alfa
Intervention Type
DRUG
Eligibility Criteria
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Inclusion Criteria
* Male \> 18 years
* Histologically proven prostate cell carcinoma
* Progression in PSA (10% elevation of nadir-value documented by two tests) at least 4 months after surgical orchiectomy or initiation of LHRH-agonist. Testosterone level must be below castration level
* All PSA values must be \> 5 ng/ml
* Haemoglobin level below 11 g/dl (6.8 mmol/l)
* Haemoglobin level tested no later than 14 days prior to randomization
* A life expectancy of more than 3 months
* Participants must sign Informed consent according to local and national regulations and European Clinical Trial Directive
* Histologically proven prostate cell carcinoma
* Progression in PSA (10% elevation of nadir-value documented by two tests) at least 4 months after surgical orchiectomy or initiation of LHRH-agonist. Testosterone level must be below castration level
* All PSA values must be \> 5 ng/ml
* Haemoglobin level below 11 g/dl (6.8 mmol/l)
* Haemoglobin level tested no later than 14 days prior to randomization
* A life expectancy of more than 3 months
* Participants must sign Informed consent according to local and national regulations and European Clinical Trial Directive
Exclusion Criteria
* Known primary haematological disorder, which could cause anaemia
* Hypertension (diastolic blood pressure \> 100 mmHg), refractory to treatment
* Symptomatic cardiovascular disease
* History of thromboembolic events during the last 12 months
* Concomitant Chemotherapy
* Active and severe liver disease
* Clinical significant inflammatory disease
* Concomitant or previous malignancies, which are likely to influence the treatment, evaluation and outcome of the current disease and therapy
* Concern of subject's compliance with the protocol procedures
* Previously included into the study
* Received erythropoietic therapy within 4 weeks before inclusion into the study
* Known positive antibody reaction to any erythropoietic agent
* Hypertension (diastolic blood pressure \> 100 mmHg), refractory to treatment
* Symptomatic cardiovascular disease
* History of thromboembolic events during the last 12 months
* Concomitant Chemotherapy
* Active and severe liver disease
* Clinical significant inflammatory disease
* Concomitant or previous malignancies, which are likely to influence the treatment, evaluation and outcome of the current disease and therapy
* Concern of subject's compliance with the protocol procedures
* Previously included into the study
* Received erythropoietic therapy within 4 weeks before inclusion into the study
* Known positive antibody reaction to any erythropoietic agent
Minimum Eligible Age
18 Years
Eligible Sex
MALE
Accepts Healthy Volunteers
No
Sponsors
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Amgen
INDUSTRY
Sponsor Role
collaborator
University of Aarhus
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Michael Borre, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Department of Urology, Aarhus University Hospital
Locations
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Department of Urology, Aarhus University Hospital
Aarhus, , Denmark
Site Status
Countries
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Denmark
References
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Aus G, Hugosson J, Norlen L. Long-term survival and mortality in prostate cancer treated with noncurative intent. J Urol. 1995 Aug;154(2 Pt 1):460-5. doi: 10.1097/00005392-199508000-00033.
Reference Type
BACKGROUND
Potosky AL, Miller BA, Albertsen PC, Kramer BS. The role of increasing detection in the rising incidence of prostate cancer. JAMA. 1995 Feb 15;273(7):548-52.
Reference Type
BACKGROUND
Borre M, Nerstrom B, Overgaard J. The dilemma of prostate cancer--a growing human and economic burden irrespective of treatment strategies. Acta Oncol. 1997;36(7):681-7. doi: 10.3109/02841869709001337.
Reference Type
BACKGROUND
Brasso K, Friis S, Kjaer SK, Iversen P. [Prostatic cancer men under age 65. Occurrence and need for study]. Ugeskr Laeger. 1997 Apr 21;159(17):2543-5. Danish.
Reference Type
BACKGROUND
Borre M, Nerstrom B, Overgaard J. The natural history of prostate carcinoma based on a Danish population treated with no intent to cure. Cancer. 1997 Sep 1;80(5):917-28.
Reference Type
BACKGROUND
Aus G, Hugosson J, Norlen L. Need for hospital care and palliative treatment for prostate cancer treated with noncurative intent. J Urol. 1995 Aug;154(2 Pt 1):466-9. doi: 10.1097/00005392-199508000-00034.
Reference Type
BACKGROUND
Otnes B, Harvei S, Fossa SD. The burden of prostate cancer from diagnosis until death. Br J Urol. 1995 Nov;76(5):587-94. doi: 10.1111/j.1464-410x.1995.tb07783.x.
Reference Type
BACKGROUND
Carlsson P, Hjertberg H, Jonsson B, Varenhorst E. The cost of prostatic cancer in a defined population. Scand J Urol Nephrol. 1989;23(2):93-6. doi: 10.3109/00365598909180819.
Reference Type
BACKGROUND
Brasso K, Friis S, Juel K, Jorgensen T, Iversen P. The need for hospital care of patients with clinically localized prostate cancer managed by noncurative intent: a population based registry study. J Urol. 2000 Apr;163(4):1150-4.
Reference Type
BACKGROUND
Strum SB, McDermed JE, Scholz MC, Johnson H, Tisman G. Anaemia associated with androgen deprivation in patients with prostate cancer receiving combined hormone blockade. Br J Urol. 1997 Jun;79(6):933-41. doi: 10.1046/j.1464-410x.1997.00234.x.
Reference Type
BACKGROUND
Ornstein DK, Beiser JA, Andriole GL. Anaemia in men receiving combined finasteride and flutamide therapy for advanced prostate cancer. BJU Int. 1999 Jan;83(1):43-6. doi: 10.1046/j.1464-410x.1999.00844.x.
Reference Type
BACKGROUND
Johansson JE, Wersall P, Brandberg Y, Andersson SO, Nordstrom L; EPO-Study Group. Efficacy of epoetin beta on hemoglobin, quality of life, and transfusion needs in patients with anemia due to hormone-refractory prostate cancer--a randomized study. Scand J Urol Nephrol. 2001 Sep;35(4):288-94. doi: 10.1080/003655901750425864.
Reference Type
BACKGROUND
Dunn A, Carter J, Carter H. Anemia at the end of life: prevalence, significance, and causes in patients receiving palliative care. J Pain Symptom Manage. 2003 Dec;26(6):1132-9. doi: 10.1016/j.jpainsymman.2003.04.001.
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BACKGROUND
Egrie JC, Browne JK. Development and characterization of novel erythropoiesis stimulating protein (NESP). Br J Cancer. 2001 Apr;84 Suppl 1(Suppl 1):3-10. doi: 10.1054/bjoc.2001.1746.
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BACKGROUND
Heatherington AC, Schuller J, Mercer AJ. Pharmacokinetics of novel erythropoiesis stimulating protein (NESP) in cancer patients: preliminary report. Br J Cancer. 2001 Apr;84 Suppl 1(Suppl 1):11-6. doi: 10.1054/bjoc.2001.1747.
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BACKGROUND
Glaspy J, Jadeja JS, Justice G, Kessler J, Richards D, Schwartzberg L, Rigas J, Kuter D, Harmon D, Prow D, Demetri G, Gordon D, Arseneau J, Saven A, Hynes H, Boccia R, O'Byrne J, Colowick AB. A dose-finding and safety study of novel erythropoiesis stimulating protein (NESP) for the treatment of anaemia in patients receiving multicycle chemotherapy. Br J Cancer. 2001 Apr;84 Suppl 1(Suppl 1):17-23. doi: 10.1054/bjoc.2001.1748.
Reference Type
BACKGROUND
Smith RE Jr, Tchekmedyian NS, Chan D, Meza LA, Northfelt DW, Patel R, Austin M, Colowick AB, Rossi G, Glaspy J. A dose- and schedule-finding study of darbepoetin alpha for the treatment of chronic anaemia of cancer. Br J Cancer. 2003 Jun 16;88(12):1851-8. doi: 10.1038/sj.bjc.6600994.
Reference Type
BACKGROUND
Bohlius J, Langensiepen S, Schwarzer G, Seidenfeld J, Piper M, Bennet C, Engert A. Erythropoietin for patients with malignant disease. Cochrane Database Syst Rev. 2004;(3):CD003407. doi: 10.1002/14651858.CD003407.pub2.
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Bohlius J, Langensiepen S, Schwarzer G, Seidenfeld J, Piper M, Bennett C, Engert A. Recombinant human erythropoietin and overall survival in cancer patients: results of a comprehensive meta-analysis. J Natl Cancer Inst. 2005 Apr 6;97(7):489-98. doi: 10.1093/jnci/dji087.
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Bohlius J, Wilson J, Seidenfeld J, Piper M, Schwarzer G, Sandercock J, Trelle S, Weingart O, Bayliss S, Djulbegovic B, Bennett CL, Langensiepen S, Hyde C, Engert A. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst. 2006 May 17;98(10):708-14. doi: 10.1093/jnci/djj189.
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Williams KJ, Parker CA, Stratford IJ. Exogenous and endogenous markers of tumour oxygenation status: definitive markers of tumour hypoxia? Adv Exp Med Biol. 2005;566:285-94. doi: 10.1007/0-387-26206-7_38.
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Varlotto J, Stevenson MA. Anemia, tumor hypoxemia, and the cancer patient. Int J Radiat Oncol Biol Phys. 2005 Sep 1;63(1):25-36. doi: 10.1016/j.ijrobp.2005.04.049.
Reference Type
BACKGROUND
Other Identifiers
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LM: 2612-3148
Identifier Type: -
Identifier Source: secondary_id
Ethical: 20060074
Identifier Type: -
Identifier Source: secondary_id
Data Protection: 2005-41-6015
Identifier Type: -
Identifier Source: secondary_id
2005-005658-37
Identifier Type: -
Identifier Source: org_study_id