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A Double-blind, Dose-response Phase II, Multicentre Study of Radium-223 (Alpharadin TM ) for the Palliation of Painful Bone Metastases in Hormone Refractory Prostate Cancer Patients

Phase 2
40 Years
Not Enrolling
Hormone Refractory Prostate Cancer, Bone Metastases

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Trial Information

A Double-blind, Dose-response Phase II, Multicentre Study of Radium-223 (Alpharadin TM ) for the Palliation of Painful Bone Metastases in Hormone Refractory Prostate Cancer Patients

The study is designed to investigate whether there is a dose-response relationship for
radium-223 in patients with painful bone metastases secondary to prostate carcinoma
regarding palliation of bone pain. The palliative efficacy will be established through
assessments of bone pain and consumption of analgesia.

Furthermore, the aim is to find the most efficient dose with an acceptable safety profile.
The safety will be assessed through measurements of adverse events, and acute haematological
toxicity during the study period. Long-term chronic toxicity, and the overall survival at
one and two years post treatment will also be assessed.

This is a double-blind, dose-response, randomized, multi-centre phase II efficacy and safety
study of radium-223. The clinical sites will enroll a total of 100 eligible patients. The
treatment is a single intravenous administration of radium-223.

The target population is patients suffering from bone pain due to skeletal metastasis
secondary to hormone refractory prostate cancer.

Inclusion Criteria

Inclusion criteria:

1. Histologically/cytologically confirmed adenocarcinoma of the prostate

2. Patient is hormone refractory with evidence of progressive disease:

- Patient must be maintained on androgen ablation therapy with LHRH agonist or
have undergone orchiectomy

- Patient's testosterone level is required to be equal to or below 50 ng/dl

- Patients in which flutamide, nilutamide, megestrol acetate, polyestradiol
phosphate, aminoglutethimide, and ketoconazole, has been recently withdrawn must
demonstrate progression of disease and be at last 4 weeks beyond the
discontinuation of such agents; for bicalutamide 6 weeks is required

- Increase in PSA levels in two consecutive measurements with at least one week
apart, demonstrating an increase over the reference (nadir) value, and with the
final PSA >/= 5 ng/ml

- A reference PSA (nadir) value must be measured at least 4 weeks after the
discontinuation of flutamide, nilutamide, megestrol acetate, polyestradiol
phosphate, aminoglutethimide, and ketoconazole, and at least 6 weeks after
discontinuation of bicalutamide

- If the third PSA value is lower than the second value, the patient could
still be eligible, provided a fourth measurement obtained at least 1 week
after the third PSA value, is grater than the second PSA value and >/= 5

3. Multifocal (>1) skeletal metastases confirmed by bone scintigraphy within 6 weeks

4. Bone pain with a score of at least 2 on BPI average pain, despite adequate use of
analgesics, that correlates with areas of increased uptake (osteoblastic activity) on
bone scintigraphy

5. Performance status: ECOG 0-2 or Karnofsky >/= 60%

6. Life expectancy: At least 3 months

7. Age more than 40 years

8. Laboratory requirements:

1. Neutrophil count >/= 1,5 x 109/L

2. Platelet count >/= 100 x109/L

3. Hemoglobin > 95 g/L

4. Bilirubin within normal institutional limits

5. ASAT and ALAT <2,5 times upper limit of normal (ULN)

9. The patient is willing and able to comply with the protocol (including maintenance of
patient diary, completion of pain assessment forms), and agrees to return to the
hospital for follow-up visits and examinations

10. The patient has been fully informed about the study and has signed the informed
consent form

Exclusion criteria

1. Has received an investigational drug within 4 weeks before the administration of
radium-223, or is scheduled to receiving one during the study period

2. Has received chemo-, immunotherapy, or external radiotherapy within the last 4 weeks
prior to entering the study, or those who have not recovered from adverse events due
to agents administered more than 4 weeks earlier

3. Has received prior hemibody external radiotherapy

4. Has received systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or
rhenium 188 for the treatment of bony metastases within the last year prior to

5. Has started treatment with bisphosphonates less than 3 months prior to administration
of study drug

6. Patients experiencing hormone withdrawal syndrome, or are of antiandrogen therapy (6 weeks for bicalutamide)

7. Patients who have started steroids or changed to treatment with steroids within the
last 4 weeks prior to administration of radium-223

8. Has other clinically significant or symptomatic disease, which might interfere with
the assessment of bone pain, e.g. spinal cord compression, compression or
infiltration of a neural plexus, nerve root or peripheral nerves

9. Other currently active (relapse within the last 3 year) malignancy (except
non-melanoma skin cancer), or known brain or visceral metastases dominating the
clinical picture of the patient

10. Other serious illness or medical condition:

- any uncontrolled infection

- cardiac failure Classification III or IV (New York Heart Association)

- Crohn disease or Ulcerative colitis

- known bone fracture within 8 weeks

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Pain Assessment (using a 100mm Visual Analogue Scale)

Outcome Time Frame:

16 weeks

Safety Issue:


Principal Investigator

Sten Nilsson, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Radiumhemmet, Karolinska University Hospital, 171 76 Stockholm, Sweden


Germany: Federal Institute for Drugs and Medical Devices

Study ID:




Start Date:

May 2005

Completion Date:

October 2009

Related Keywords:

  • Hormone Refractory Prostate Cancer
  • Bone Metastases
  • Hormone Refractory Prostate Cancer
  • Bone Metastases
  • Radium-223
  • Palliation of bone pain
  • Neoplasm Metastasis
  • Neoplasms, Second Primary
  • Prostatic Neoplasms
  • Bone Neoplasms
  • Bone Marrow Diseases