BAY88-8223, Dose Finding Study in Patients With HRPC

A Double Blind, Randomised, Dose Finding, Repeat Dose, Phase II, Multicentre Study of Alpharadin® for the Treatment of Patients With Hormone Refractory Prostate Cancer and Skeletal Metastases

The purpose of this study is to evaluate the effectiveness of the investigational radioisotope Radium-223, Alpharadin, in treatment of men with prostate cancer and bone metastases that no longer respond to hormonal treatment.

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate.

• Hormone refractory with evidence of rising PSA:

  • Patient must be maintained on androgen ablation therapy with LHRH agonist (stable dose for at least 8 weeks prior to study entry), or have undergone orchiectomy

  • Serum testosterone level is required to be ≤ 50 ng/dl

  • Patients who have received prior hormonal drug therapy:

    • Flutamide, nilutamide or cyproterone acetate must have stopped at least four weeks prior to study drug administration and progression must have been demonstrated since cessation;
    • Bicalutamide must have stopped at least six weeks prior to study drug administration and progression must have been demonstrated since cessation

  • Elevated and rising PSA:

    • Baseline PSA level ≥ 10 ng/ml
    • Progressive rise in PSA, defined as two consecutive increases in PSA documented over a previous reference value (measure 1). The first increase in PSA (measure 2) should occur a minimum of 1 week from the reference value (measure 1. This increase in PSA should be confirmed (measure 3) after a minimum of 1 week. If the confirmatory PSA value (measure 3) is less than the previous value, the patient will still be eligible provided the next PSA measure (measure 4)is found to be greater than the second PSA value(measure 2).3. Multifocal skeletal metastases confirmed by bone scintigraphy within the last 6 weeks

• Performance status: ECOG 0-2

• Life expectancy: At least 6 months

• Laboratory requirements:

  • Neutrophil count ≥ 1.5 x 109/L
  • Platelet count ≥ 100 x109/L
  • Haemoglobin ≥ 95 g/L
  • Total bilirubin level within normal institutional limits
  • ASAT and ALAT ≤ 2,5 times upper institutional limit of the normal range

• The patient is willing and able to comply with the protocol (including maintenance of patient diary), and agrees to return to the hospital for follow-up visits and examination

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

Exclusion Criteria:

• Has received an investigational drug within 4 weeks prior to the administration of radium-223, or is scheduled to receive one during the treatment and post-treatment period

• Has received chemo-, immunotherapy, or external radiotherapy within the last 4 weeks prior to administration of study drug, or has not recovered from adverse events due to agents administered more than 4 weeks earlier

• More than one regimen of previous cytotoxic chemotherapy

• Has received prior hemibody external radiotherapy

• Has a need for immediate external radiotherapy

• 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 administration of study drug

• Has started treatment with bisphosphonates less than 3 months prior to administration of study drug. Patients are allowed to be on bisphosphonates provided patient is on a stable dose for ≥ 12 weeks before administration of study drug.

• Patients who are ≤ 4 weeks (6 weeks for bicalutamide) post withdrawal of antiandrogen therapy

• Patients who have started or stopped systemic steroids, within a week prior to study drug administration

• Other currently active (relapse within the last 3 years) malignancy (except non-melanoma skin cancer) that are not prostate cancer metastases

• Visceral metastases from prostate cancer as assessed by abdominal/pelvic CT or MRI within six weeks before administration of study drug; Lung lesions from prostate cancer as assessed by chest X-ray within 6 weeks. This requirement does not include abdominal or pelvic lymph node involvement (individual lymph node size must not exceed 1 cm in short diameter) which is acceptable

• Bulky loco-regional disease

• Any other serious illness or medical condition, for example:

  • any uncontrolled infection
  • any patient who has clinical heart failure severe enough to cause marked limitation of activity, and who is only comfortable at rest; or any patient who has heart failure more severe than this (NYHA Heart Failure Class III or IV
  • Crohns disease or ulcerative colitis