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.

Study Overview

• Status: Completed
• Conditions: Neoplasm Metastasis; Prostate Cancer
• Intervention / Treatment: Drug: Radium-223 dichloride (BAY88-8223)

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5RT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radium-223 dichloride (Xofigo, BAY88-8223) Dose group 1; 25 kBq/kg b.w., 3 times at 6 week intervals	Drug: Radium-223 dichloride (BAY88-8223); 3 doses of radium-223 at different dose levels, 25, 50 or 80 kBq/kg b.w.given as injection.
Experimental: Radium-223 dichloride (Xofigo, BAY88-8223) Dose group 2; 50 kBq/kg b.w., 3 times at 6 week intervals	Drug: Radium-223 dichloride (BAY88-8223); 3 doses of radium-223 at different dose levels, 25, 50 or 80 kBq/kg b.w.given as injection.
Experimental: Radium-223 dichloride (Xofigo, BAY88-8223) Dose group 3; 80 kBq/kg b.w., 3 times at 6 week intervals	Drug: Radium-223 dichloride (BAY88-8223); 3 doses of radium-223 at different dose levels, 25, 50 or 80 kBq/kg b.w.given as injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants in each dose group with a confirmed PSA response	PSA response; each patient will be classified as PSA responder/non-responder according to the definition of PSA response:a decrease from baseline of at least 50% maintained for at least three weeks.	24 weeks, 12 months, 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
The maximum percent decrease in PSA level compared to baseline	24 weeks, 12 months, 24 months
Time to PSA Progression	24 weeks, 12 months, 24 months
Bone-ALP response (classified as for PSA response) and decrease in bone-ALP level compared to baseline	24 weeks, 12 months, 24 months
Total number of SRE per patient	24 weeks, 12 months, 24months
Pain Assessment and analgesic consumption	24 weeks, 12 months, 24months
Time to death from first treatment	24 weeks, 12 months, 24months
Time to Skeletal Related Events (SRE)	24 weeks, 12 months, 24 months
Adverse events, blood chemistry and haematological toxicity	24 weeks, 12 months, 24 months

Collaborators and Investigators

• Sponsor: Bayer
• Investigators: Study Director: Bayer Study Director, Bayer

Publications and helpful links

General Publications

• Parker CC, Pascoe S, Chodacki A, O'Sullivan JM, Germa JR, O'Bryan-Tear CG, Haider T, Hoskin P. A randomized, double-blind, dose-finding, multicenter, phase 2 study of radium chloride (Ra 223) in patients with bone metastases and castration-resistant prostate cancer. Eur Urol. 2013 Feb;63(2):189-97. doi: 10.1016/j.eururo.2012.09.008. Epub 2012 Sep 13.

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: June 13, 2006
• First Submitted That Met QC Criteria: June 14, 2006
• First Posted (Estimated): June 15, 2006

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Recurrent Prostate Cancer; metastatic Cancer
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Neoplastic Processes; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Neoplasm Metastasis; Antineoplastic Agents; Radium Ra 223 dichloride
• Other Study ID Numbers: 15304; 2005-003680-22 (EudraCT Number); BC1-04 (Other Identifier: Algeta ASA)