NCT01798108

Brief Summary

A new bone-seeking radiopharmaceutical drug, called Radium-223 dichloride (formerly known as "Alpharadin"), is currently under development. It is an injectable aqueous solution containing radium-223, a radionuclide that emits radiation of another quality and with a different distribution than radiopharmaceuticals currently in use. After injection of the drug into the blood, a large portion of the drug will accumulate in the bones, and irradiate the skeletal metastases. The drug is expected to be retained longer in the painful sites of bone than in other sites of the body, and may alleviate pain through its radiation. Radium-223 is expected to be both efficacious as regards the targeted localised irradiation, and also to have a favourable safety profile. The radiopharmaceutical drug Radium-223 has not been given to humans before. In this first clinical study in man, a so-called phase I study, the safety, tolerance and the toxicity of various radioactivity doses of Radium-223 will be evaluated.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
31

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Aug 2001

Geographic Reach
2 countries

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 14, 2001

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 25, 2003

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 25, 2003

Completed
9.6 years until next milestone

First Submitted

Initial submission to the registry

January 10, 2013

Completed
2 months until next milestone

First Posted

Study publicly available on registry

February 25, 2013

Completed
Last Updated

May 19, 2017

Status Verified

May 1, 2017

Enrollment Period

1.9 years

First QC Date

January 10, 2013

Last Update Submit

May 18, 2017

Conditions

Neoplasm Metastasis

Keywords

Advanced skeletal metastasesRadium-223Radium-223 dichlorideAlpharadin

Outcome Measures

Primary Outcomes (1)

  • Number of participants with predetermined adverse events (dose limiting toxicity [DLT]) as a measure of safety and tolerability while dose escalating

    Up to 8 weeks from injection

Secondary Outcomes (2)

  • Blood clearance of radioactivity

    48 hours after the last injection

  • Quality of Life Questionnaire

    8 weeks after the last injection

Study Arms (1)

Radium-223 dichloride

EXPERIMENTAL

The study had 2 parts. Part 1a was designed with single injections of Radium-223 given to cohorts of 5 patients for each of 5 pre-defined dose levels. Part 1b was designed to retreat and fractionate the dose of Radium-223 in multiple injections.Based on the revised correction factor by calibration, recalculations verified that the single injection doses administered in the part 1a were : 46, 93, 163, 213 and 250 kBq/kg b.w. Two re-treated patients (dose group 6) received a second dose that resulted in a total dose of 250 kBq/kg b.w. The fractionated doses were 1/5 and ½ of the highest dose in part1b (i.e. 250kBq so 5 x 50 and 2 x 125 kBq/kg b.w. respectively).

Radiation: Radium-223 dichloride (BAY88-8223)

Interventions

Radium-223 dichloride (BAY88-8223)RADIATION

\- Single injection. Starting dose 46 kBq/kg b.w. Escalating doses 93, 163, 213 and 250 kBq/kg b.w. (9.8.2 Changes in addition to those described in amendments) After completion of the five dose levels above, the protocol was amended and the study extended to include patients to received multiple injections of Radium-223 - Re-treatment: Patients who had earlier been included in the study and received dose levels 46, 93 or 163 kBq/kg b.w. could be given a second injection, provided that the total dose did not exceed 250 kBq/kg b.w. - Fractionated dose (multiple dosing) Patients were given multiple injections in treatment: 5 injections of 50 kBq/kg b.w. at 3 weeks intervals. Patients were given multiple injections in treatment: 2 injections of 125 kBq/kg b.w. at 6 weeks interval

Radium-223 dichloride

Eligibility Criteria

Age30 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ≥ 30 years of age
  • has histologically or cytologically confirmed breast or prostate carcinoma
  • presents with bony metastases, confirmed by scintigraphic imaging within the previous 4 weeks
  • relapsing with new foci in the skeleton after previous external radiotherapy
  • has a life expectancy of at least 8 weeks (study part Ia), 5 months for study part Ib
  • good performance status; ECOG (Eastern Cooperative Oncology Group) status 0-2
  • has normal bone marrow, hepatic, renal and cardiac functions
  • clinical chemical laboratory values are within pre-specified range, measured within 7 days prior to dosing day
  • for female patients: post-menopausal, surgically sterile or taking adequate contraceptive precaution

You may not qualify if:

  • has previously been included in this study. This criterion is applicable for patients that receive a single injection of the study drug, but not for patients to be re-treated, or for those to receive a fractionated dosing regimen (study part Ib).
  • has received an investigational drug in the 4 weeks before or is scheduled to receiving one during or in the 8 weeks after study drug administration. This criterion is applicable for patients that receive a single injection of the study drug and for patients to be re-treated.
  • has received any other investigational drug than radium-223 in the 4 weeks before first injection of study drug or is scheduled to receiving one during or in the 8 weeks after the fractionated study drug regimen. This criterion is applicable for patients receiving fractionated dose of the study drug.
  • has received chemo-, immuno-, or radiotherapy within the last 4 weeks prior to entry in the study
  • has other active, serious, life-threatening disease with a life expectancy of less than 8 weeks
  • has any uncontrolled infection
  • requires oxygen for pulmonary metastases
  • has poor renal function with S-Creatinine \>150 mmol/L (males), \>100 mmol/L (females)
  • has heart insufficiency, Class III or IV NYHA (New York Heart Association)
  • is pregnant or lactating
  • for female patients: of childbearing potential, and not taking adequate contraceptive measures

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

The Norwegian Radium Hospital

Oslo, Norway

Location

University Hospital of North Norway

Tromsø, Norway

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Related Publications (1)

  • Nilsson S, Larsen RH, Fossa SD, Balteskard L, Borch KW, Westlin JE, Salberg G, Bruland OS. First clinical experience with alpha-emitting radium-223 in the treatment of skeletal metastases. Clin Cancer Res. 2005 Jun 15;11(12):4451-9. doi: 10.1158/1078-0432.CCR-04-2244.

    PMID: 15958630BACKGROUND

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

radium Ra 223 dichloride

Condition Hierarchy (Ancestors)

Neoplastic ProcessesNeoplasmsPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Bayer Study Director

    Bayer

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
OTHER
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 10, 2013

First Posted

February 25, 2013

Study Start

August 14, 2001

Primary Completion

June 25, 2003

Study Completion

June 25, 2003

Last Updated

May 19, 2017

Record last verified: 2017-05

Locations

SE(1)NO(2)