Effect of Darbepoetin Alfa (Aranesp®) on Anemia in Patients With Advanced Hormone Independent Prostate Cancer

Anemia Clinical Trial

Official title:

A Randomized, Multi-center Study to Assess the Effect of Darbepoetin Alfa (Aranesp®) for the Treatment of Anemia in Patients With Advanced Hormone Independent Prostate Cancer and Anaemia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00381836
• Other study ID #: 2005-005658-37
• Secondary ID: LM: 2612-3148Eth
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: September 27, 2006
• Last updated: December 3, 2015
• Start date: October 2006
• Est. completion date: February 2007

Study information

• Verified date: February 2008
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyDenmark: The Regional Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 140
• Est. completion date: February 2007
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Anemia
• Prostatic Neoplasms

Intervention

Drug:
• Darbepoetin Alfa

Locations

Country	Name	City	State
Denmark	Department of Urology, Aarhus University Hospital	Aarhus

Sponsors (2)

Lead Sponsor	Collaborator
University of Aarhus	Amgen

Country where clinical trial is conducted

Denmark, 

References & Publications (22)

Aus G, Hugosson J, Norlén L. Long-term survival and mortality in prostate cancer treated with noncurative intent. J Urol. 1995 Aug;154(2 Pt 1):460-5. Review. — View Citation

Aus G, Hugosson J, Norlén 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. — View Citation

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. Review. Update in: Cochrane Database Syst Rev. 2006;(3):CD003407. — View Citation

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. Review. — View Citation

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. Review. — View Citation

Borre M, Nerstrøm 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. — View Citation

Borre M, Nerstrøm 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. — View Citation

Brasso K, Friis S, Juel K, Jørgensen 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. — View Citation

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. — View Citation

Carlsson P, Hjertberg H, Jönsson B, Varenhorst E. The cost of prostatic cancer in a defined population. Scand J Urol Nephrol. 1989;23(2):93-6. — View Citation

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. — View Citation

Egrie JC, Browne JK. Development and characterization of novel erythropoiesis stimulating protein (NESP). Br J Cancer. 2001 Apr;84 Suppl 1:3-10. Review. — View Citation

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 1:17-23. — View Citation

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 1:11-6. — View Citation

Johansson JE, Wersäll P, Brandberg Y, Andersson SO, Nordström 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. — View Citation

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. — View Citation

Otnes B, Harvei S, Fosså SD. The burden of prostate cancer from diagnosis until death. Br J Urol. 1995 Nov;76(5):587-94. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Varlotto J, Stevenson MA. Anemia, tumor hypoxemia, and the cancer patient. Int J Radiat Oncol Biol Phys. 2005 Sep 1;63(1):25-36. Review. — View Citation

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. Review. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The haematopoietic response at week 4, 8, 12, 16 and 20
Secondary	Quality of Life (EQ-5D and QLQ-C30) at week 8 and 20
Secondary	Number of blood transfusions at week 4, 8, 12, 16 and 20
Secondary	Change in haemoglobin at week 4, 8, 12, 16 and 20
Secondary	Number of days admitted to hospital during the 20 week study period