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Dose Escalation Study of Radium-223 Dichloride in Patients With Advanced Skeletal Metastases

Primary Purpose

Neoplasm Metastasis

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Radium-223 dichloride (BAY88-8223)

About this trial

This is an interventional other trial for Neoplasm Metastasis focused on measuring Advanced skeletal metastases, Radium-223, Radium-223 dichloride, Alpharadin

Eligibility Criteria

30 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

≥ 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

Exclusion Criteria:

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

Sites / Locations

The Norwegian Radium Hospital
University Hospital of North Norway
Karolinska University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Radium-223 dichloride

Arm Description

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).

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Blood clearance of radioactivity

Quality of Life Questionnaire

Full Information

NCT ID

NCT01798108

First Posted

January 10, 2013

Last Updated

May 18, 2017

Sponsor

Bayer

1. Study Identification

Unique Protocol Identification Number

NCT01798108

Brief Title

Dose Escalation Study of Radium-223 Dichloride in Patients With Advanced Skeletal Metastases

Official Title

A Phase I Open-label, Multicenter, Dose-escalating Study of Radium-223 in Patients With Advanced Skeletal Metastases

Study Type

Interventional

2. Study Status

Record Verification Date

May 2017

Overall Recruitment Status

Completed

Study Start Date

August 14, 2001 (Actual)

Primary Completion Date

June 25, 2003 (Actual)

Study Completion Date

June 25, 2003 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bayer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neoplasm Metastasis

Keywords

Advanced skeletal metastases, Radium-223, Radium-223 dichloride, Alpharadin

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

31 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Radium-223 dichloride

Arm Type

Experimental

Arm Description

Intervention Type

Radiation

Intervention Name(s)

Radium-223 dichloride (BAY88-8223)

Intervention Description

- 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

Primary Outcome Measure Information:

Title

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

Time Frame

Up to 8 weeks from injection

Secondary Outcome Measure Information:

Title

Blood clearance of radioactivity

Time Frame

48 hours after the last injection

Title

Quality of Life Questionnaire

Time Frame

8 weeks after the last injection

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: ≥ 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 Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bayer Study Director

Organizational Affiliation

Bayer

Official's Role

Study Director

Facility Information:

Facility Name

The Norwegian Radium Hospital

City

Oslo

Country

Norway

Facility Name

University Hospital of North Norway

City

Tromsoe

Country

Norway

Facility Name

Karolinska University Hospital

City

Stockholm

Country

Sweden

12. IPD Sharing Statement

Citations:

PubMed Identifier

15958630

Citation

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.

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Dose Escalation Study of Radium-223 Dichloride in Patients With Advanced Skeletal Metastases

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