Radium-223 in Patients With Hormone Refractory Prostate Cancer (HRPC) and Skeletal Metastases

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00667537
First received: April 24, 2008
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
Hormone Refractory Prostate Cancer
Bone Metastases
Drug: Alpharadin TM (Radium-223)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Phase I Open-label, Dosimetry, Biodistribution and Pharmacokinetic Study of Alpharadin™ in Patients With Hormone Refractory Prostate Cancer and Skeletal Metastases

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Estimation of whole-body retention of radioactivity at each imaging time post-injection [ Time Frame: 1 week ] [ Designated as safety issue: No ]
  • Radiation Dosimetry: Estimation of the individual organ uptake/retention of radioactivity at each time-point post injection [ Time Frame: 1 week ] [ Designated as safety issue: No ]
  • Estimate retention of administered radioactivity in blood [ Time Frame: 2 days ] [ Designated as safety issue: No ]
  • Estimation of elimination of radioactivity in urine and faeces [ Time Frame: 2 days ] [ Designated as safety issue: No ]
  • Radiation Dosimetry: Calculation of estimated absorbed radiation dose to target organs [ Time Frame: 1 week ] [ Designated as safety issue: No ]
  • Pharmacokinetics [ Time Frame: 1 week ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Imaging: Comparison of the biodistribution and dosimetry after the first and second injection [ Time Frame: 7 weeks ] [ Designated as safety issue: No ]
  • Safety: Adverse events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Safety: Laboratory variables; serum biochemistry and haematology [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Safety: Vital signs (systolic/diastolic blood pressure, respiratory rate, heart rate and body temperature) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Safety: ECG (12 leads) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Safety: Physical examination [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 6
Study Start Date: July 2007
Study Completion Date: December 2009
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1 Drug: Alpharadin TM (Radium-223)
IV administrations of 100 kBq/kg b.w. Two administrations will take place with an interval of 6 weeks.

Detailed Description:

This is an open-label, biodistribution, radiation dosimetry, pharmacokinetic, safety and efficacy study of Alpharadin treatment. The treatment consists of at least two intravenous administrations of Alpharadin.

The target population is patients with asymptomatic or symptomatic (e.g. bone pain) hormone refractory prostate cancer, with documented skeletal metastases.

The study is designed to investigate safety, biodistribution, radiation dosimetry and pharmacokinetics of two separate IV administrations of Alpharadin (100 kBq/kg b.w.) separated by six weeks.

Furthermore, the secondary objectives of the study are:

  • To evaluate treatment response (antitumor effect in osteoblastic bone metastases) of Alpharadin treatment consisting of two injections of activity 100 kBq/kg b.w. 6 weeks apart
  • To evaluate long-term radiation toxicity
  • Survival data will be collected at 6 and 12 months after the first injection
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically confirmed adenocarcinoma of the prostate.
  2. 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 bilateral orchiectomy
    • Serum testosterone level is required to be </=50 ng/dl
    • Patients who have received prior antiandrogen drug therapy:

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

      • 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 at 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. Skeletal metastases confirmed by bone scintigraphy within the last 6 weeks
  4. Performance status: ECOG 0-2
  5. Life expectancy: >/= 6 months
  6. 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
    • S-Creatinine </= 1,5 times upper institutional limit of the normal range
  7. The patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow-up visits and examination
  8. Able and willing to give written informed consent.

Exclusion Criteria:

  1. 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
  2. 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
  3. More than one regimen of previous cytotoxic chemotherapy
  4. Has received prior hemibody external radiotherapy
  5. Has a need for immediate external radiotherapy
  6. Has received systemic radiotherapy with radium-223, 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.
  7. 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.
  8. Patients who are </= 4 weeks (6 weeks for bicalutamide) post withdrawal of antiandrogen therapy
  9. Patients who have started or stopped systemic steroids, within a week prior to study drug administration, or are expected to be subject to changes in the systemic steroid medication
  10. Other currently active (relapse within the last 3 years) malignancy (except non-melanoma skin cancer) that are not prostate cancer metastases
  11. Visceral (e.g. liver, lung) metastases from prostate cancer as assessed by abdominal/ pelvic CT or chest radiograph within six weeks before administration of study drug;
  12. Lymph node metastases with short-axis diameter greater than 2 cm.
  13. Bulky loco-regional disease
  14. 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00667537

Locations
United Kingdom
Institute of Cancer Research and Royal Marsden Hospital
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00667537     History of Changes
Other Study ID Numbers: 15302, BC1-05
Study First Received: April 24, 2008
Last Updated: July 21, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Bayer:
Hormone Refractory Prostate Cancer
Bone Metastases
Radium-223
Biodistribution
Dosimetry
Pharmacokinetics

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Prostatic Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014