Bone MetastasesPhase 1/2NCT01106352

A Study of Alpharadin With Docetaxel in Patients With Bone Metastasis From Castration-Resistant Prostate Cancer (CRPC)

A Phase 1/2 study testing Radium-223 dichloride (Xofigo, BAY88-8223) and Docetaxel in people with Bone Metastases and Castration-Resistant Prostate Cancer, run by Bayer at 7 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The main purpose of this study is to establish a recommended dose of Alpharadin to be used in combination with docetaxel in patients with bone metastases from castration-resistant prostate cancer and to investigate safety and explore efficacy of the recommended dose. Read more about this study

Who is it for?: Ages 18 years and older, men only
Conditions the study is for: Bone Metastases, Castration-Resistant Prostate Cancer
What is being tested?: Radium-223 dichloride (Xofigo, BAY88-8223) and Docetaxel
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 70 participants
Where: 7 sitesin 2 countries
Study dates: Jul 2010to Jun 2015
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Men only
No healthy volunteers
Adult, Older adult

Who may be able to join

Histologically or cytologically confirmed adenocarcinoma of the prostate.
Two or more bone metastases (hot spots) confirmed by bone scintigraphy within 8 weeks prior to study entry
Known castration-resistant disease
Karnofsky Performance Status (KPS): ≥70% within 14 days before start of study treatment (ECOG 1)
Life expectancy at least 6 months.
Acceptable hematology and serum biochemistry screening values
Eligible for use of docetaxel according to the product information (package insert or similar).

Who cannot join

Has received an investigational therapeutic drug within the last 4 weeks prior to start of study treatment, or is scheduled to receive one during the treatment period.
Has received external radiotherapy within the last 4 weeks prior to start of study treatment.
Has an immediate need for radiotherapy.
Has received prior hemibody external radiotherapy .
Has received systemic radiotherapy (e.g. samarium, strontium etc.) for the treatment of bone metastases.
Has received cytotoxic chemotherapy within the last 4 weeks prior to start of study treatment, or has not recovered to grade 1 or 0 from adverse events due to cytotoxic chemotherapy administered more than 4 weeks earlier.

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Has received more than ten previous infusions of docetaxel.
Previous known experience of grade ≥ 3 docetaxel related toxicities or docetaxel toxicity related dose interruption or discontinuation.
Previous use of G-CSF for persistent neutropenia after docetaxel treatment.
Has received blood transfusion or erythropoietin (EPO) within the last 4 weeks prior to start of study treatment.
Has received prior treatment with Alpharadin.
Malignant lymphadenopathy exceeding 3 cm in short-axis diameter.
Symptomatic nodal disease, i.e. scrotal, penile or leg edema.
Visceral metastases from CRPC (>2 lung and/or liver metastases [size ≥2cm]), as assessed by CT scan or MRI of the chest/abdomen/pelvis within the last 8 weeks prior to start of study treatment.
Uncontrolled loco-regional disease.
Other primary tumor (other than CRPC) including haematological malignancy present within the last 5 years (except non-melanoma skin cancer or low-grade superficial bladder cancer).
Has imminent or established spinal cord compression based on clinical findings and/or MRI.
Unmanageable fecal incontinence

Trial locations and contacts

7 sites in 2 countries.

Country

City, postcode or hospital

7 sites in 2 countries

United States6 sites

Study site
Baltimore, Maryland, 21287
Study site
Boston, Massachusetts, 02115-6013
Study site
Evanston, Illinois, 60201
Study site
New York, New York, 10065
Study site
San Francisco, California, 94115
Study site
Seattle, Washington, 98109

Other trials in United States

France1 site

Study site
Villejuif, 94805

Other trials in France

About this study

Official title: A Phase I/IIa Study of Safety and Efficacy of Alpharadin® With Docetaxel in Patients With Bone Metastasis From Castration-Resistant Prostate Cancer

Read the detailed description

The trial was initially conducted and submitted by Algeta ASA. After acquiring Algeta, Bayer is now the sponsor.

Conditions: Bone Metastases, Castration-Resistant Prostate Cancer
Being tested: Radium-223 dichloride (Xofigo, BAY88-8223), Docetaxel
Keywords: The target population is patients with bone metastasis from castration-resistant prostate cancer intended for treatment with docetaxel

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Radium-223 dichloride (Xofigo, BAY88-8223)Drug
Alpharadin (Radium-223 dichloride) is administered intravenously as a bolus injection.
DocetaxelDrug
Docetaxel (75 mg/m^2) will be administered intravenously every 3 weeks with 5 mg prednisone twice a day continuously and pre-medication with dexamethasone. Step-down to 60 mg/m^2 is allowed as per the approved docetaxel label.

Study groups in NCT01106352
Study group	Role	What they receive
Radium-223 dichloride (Xofigo, BAY88-8223) + docetaxel	Experimental	Alpharadin (Radium-223 dichloride) is administered intravenously as a bolus injection. In the randomized phase IIa part of the protocol, the dose established in the dose-escalation part of the protocol (Phase I) will be used, i.e. 5 doses of 50 kBq/kg b.w. every 6 weeks in combination with the approved step-down dose of docetaxel (60 mg/m^2) administered intravenously every 3 weeks with 5 mg prednisone twice a day continuously and pre-medication with dexamethasone. Receives: Drug: Radium-223 dichloride (Xofigo, BAY88-8223); Drug: Docetaxel
Docetaxel	Active comparator	Docetaxel (75 mg/m2) will be administered intravenously every 3 weeks with 5 mg prednisone twice a day continuously and pre-medication with dexamethasone. Step-down to 60 mg/m^2 is allowed as per the approved docetaxel label. Receives: Drug: Docetaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Subjects With Dose-Limiting Toxicities - Dose Escalation Part
DLT was defined as - Absolute neutrophil count grade greater than or equal to (>=) 4 (Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0: less than [<] 0.5 × 109 per Liter) lasting longer than 7 days without fever despite granulocyte colony-stimulating factor (G-CSF) support). Platelet count Grade >= 4 (CTCAE, v4.0: < 25× 109/L) lasting longer than 7 days. Diarrhea Grade >= 3 (CTAE, v4.0: increase of >= 7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared with baseline; limiting self-care in activities of daily living) in spite of optimal use of antidiarrheal medication. Vomiting or constipation Grade >= 4 (CTCAE, v4.0: life-threatening consequences; urgent intervention indicated). Febrile neutropenia Grade >= 3 (CTCAE, v4.0).
Measured: From randomization until 6 weeks post-injection in all dose cohort of dose-escalation part
Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Treatment-Emergent Serious Adverse Events (TESAE) With a CTCAE Grade of 3 or 4
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An Serious Adverse Event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in patient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Measured: From start of study treatment to 6 weeks after study treatment (that is maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort) and 8 weeks for serious AEs
Change From Baseline in Serum Biochemistry (Albumin, Protein, Hemoglobin) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Measured: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
Change From Baseline in Serum Biochemistry (Alkaline Phosphatase [AP], Alanine Aminotransferase [AAT], Lactate Dehydrogenase [LD]) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Measured: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
Change From Baseline in Serum Biochemistry (Bilirubin, Creatinine) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Measured: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
Change From Baseline in Serum Biochemistry (Calcium, Chloride, Magnesium, Potassium, Phosphate, Sodium, Urea) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Measured: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
Change From Baseline in Serum Biochemistry (Platelets, Leukocytes, Lymphocytes, Neutrophils, Monocytes, Eosinophils, Basophils) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Measured: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
Change From Baseline in Serum Biochemistry (Erythrocytes) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Measured: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
Changes From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Measured: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
Changes From Baseline in Respiratory Rate During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Measured: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
Changes From Baseline in Heart Rate During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Measured: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
Changes From Baseline in Weight During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Measured: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
Number of Subjects With Physical Examination During the Treatment Period
Any physical examination finding that was classified by the investigator as a clinically significant change (compared with previous examination) was considered an AE, documented on the eCRF, and followed until the outcome was known. The below physical examination findings were recorded and reported. GDASC = General disorders and administration site conditions MND = Metabolism and nutrition disorders SSTD= Skin and subcutaneous tissue disorders MCTD = Musculoskeletal and connective tissue disorders IPPC = Injury, poisoning and procedural complications RTMD = Respiratory, thoracic and mediastinal disorders NBMU = Neoplasms benign, malignant and unspecified (include cysts and polyps) In the below table.
Measured: From start of study treatment to 6 weeks after study treatment (i.e., maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
Number of Subjects With Signs of Long-Term Radiation Toxicity
Long-term radiation toxicity included incidence of potential late toxicity, such as new primary cancers and bone marrow changes (acute myelogenous leukemia, myelodysplastic syndrome, and aplastic anemia).
Measured: From start of study treatment upto 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2010Jun 2015

First posted19 Apr 2010 (estimated)
Study startJul 2010
Primary completionJun 2015
Study completionJun 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Bone MetastasesStudies of the same condition, open and under way.
More trials run by BayerThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 70 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01106352
Sponsor's protocol ID: 15469
Other IDs: BC1-10, 2011-000822-31
Status last verified: Nov 2016
First submitted: 16 Apr 2010
Last updated: 4 Jan 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Morris MJ, Loriot Y, Sweeney CJ, Fizazi K, Ryan CJ, Shevrin DH, Antonarakis ES, Pandit-Taskar N, Deandreis D, Jacene HA, Vesselle H, Petrenciuc O, Lu C, Carrasquillo JA, Higano CS. Radium-223 in combination with docetaxel in patients with castration-resistant prostate cancer and bone metastases: a phase 1 dose escalation/randomised phase 2a trial. Eur J Cancer. 2019 Jun;114:107-116. doi: 10.1016/j.ejca.2019.04.007. Epub 2019 May 11.
PubMed 31082669
Gkialas IK, Fragkoulis C. Emerging therapies targeting castration-resistant prostate cancer. J BUON. 2015 Nov-Dec;20(6):1389-96.
PubMed 26854432

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 4 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/IIa Study of Safety and Efficacy of Alpharadin® With Docetaxel in Patients With Bone Metastasis From Castration-Resistant Prostate Cancer
ClinicalTrials.gov ID: NCT01106352
Acronym / sponsor ID: 15469
Conditions: Bone Metastases, Castration-Resistant Prostate Cancer
Keywords: The target population is patients with bone metastasis from castration-resistant prostate cancer intended for treatment with docetaxel
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 70 participants (actual)
Lead sponsor: BayerIndustry (pharma, biotech, devices)
Study start: Jul 2010
Primary completion: Jun 2015 (actual)
Study completion: Jun 2015 (actual)
First posted: 19 Apr 2010 (estimated)
Results: Posted 9 Nov 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The trial was initially conducted and submitted by Algeta ASA. After acquiring Algeta, Bayer is now the sponsor.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Radium-223 dichloride (Xofigo, BAY88-8223) + docetaxel	Experimental	Drug: Radium-223 dichloride (Xofigo, BAY88-8223), Drug: DocetaxelAlpharadin (Radium-223 dichloride) is administered intravenously as a bolus injection. In the randomized phase IIa part of the protocol, the dose established in the dose-escalation part of the protocol (Phase I) will be used, i.e. 5 doses of 50 kBq/kg b.w. every 6 weeks in combination with the approved step-down dose of docetaxel (60 mg/m^2) administered intravenously every 3 weeks with 5 mg prednisone twice a day continuously and pre-medication with dexamethasone.
Docetaxel	Active comparator	Drug: DocetaxelDocetaxel (75 mg/m2) will be administered intravenously every 3 weeks with 5 mg prednisone twice a day continuously and pre-medication with dexamethasone. Step-down to 60 mg/m^2 is allowed as per the approved docetaxel label.

Who may qualify

Ages: 18 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Histologically or cytologically confirmed adenocarcinoma of the prostate.
Two or more bone metastases (hot spots) confirmed by bone scintigraphy within 8 weeks prior to study entry
Known castration-resistant disease
Karnofsky Performance Status (KPS): ≥70% within 14 days before start of study treatment (ECOG 1)
Life expectancy at least 6 months.

Key exclusion criteria (18 listed)

Has received an investigational therapeutic drug within the last 4 weeks prior to start of study treatment, or is scheduled to receive one during the treatment period.
Has received external radiotherapy within the last 4 weeks prior to start of study treatment.
Has an immediate need for radiotherapy.
Has received prior hemibody external radiotherapy .
Has received systemic radiotherapy (e.g. samarium, strontium etc.) for the treatment of bone metastases.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Radium-223 dichloride (Xofigo, BAY88-8223)Alpharadin (Radium-223 dichloride) is administered intravenously as a bolus injection.	Drug	Radium-223 dichloride (Xofigo, BAY88-8223) + docetaxel
DocetaxelDocetaxel (75 mg/m^2) will be administered intravenously every 3 weeks with 5 mg prednisone twice a day continuously and pre-medication with dexamethasone. Step-down to 60 mg/m^2 is allowed as per the approved docetaxel label.	Drug	Docetaxel, Radium-223 dichloride (Xofigo, BAY88-8223) + docetaxel

Primary outcome

Number of Subjects With Dose-Limiting Toxicities - Dose Escalation Part
Time frame: From randomization until 6 weeks post-injection in all dose cohort of dose-escalation part
DLT was defined as - Absolute neutrophil count grade greater than or equal to (>=) 4 (Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0: less than [<] 0.5 × 109 per Liter) lasting longer than 7 days without fever despite granulocyte colony-stimulating factor (G-CSF) support). Platelet count Grade >= 4 (CTCAE, v4.0: < 25× 109/L) lasting longer than 7 days. Diarrhea Grade >= 3 (CTAE, v4.0: increase of >= 7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared with baseline; limiting self-care in activities of daily living) in spite of optimal use of antidiarrheal medication. Vomiting or constipation Grade >= 4 (CTCAE, v4.0: life-threatening consequences; urgent intervention indicated). Febrile neutropenia Grade >= 3 (CTCAE, v4.0).
Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Treatment-Emergent Serious Adverse Events (TESAE) With a CTCAE Grade of 3 or 4
Time frame: From start of study treatment to 6 weeks after study treatment (that is maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort) and 8 weeks for serious AEs
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An Serious Adverse Event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in patient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Change From Baseline in Serum Biochemistry (Albumin, Protein, Hemoglobin) During the Treatment Period
Time frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Change From Baseline in Serum Biochemistry (Alkaline Phosphatase [AP], Alanine Aminotransferase [AAT], Lactate Dehydrogenase [LD]) During the Treatment Period
Time frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Change From Baseline in Serum Biochemistry (Bilirubin, Creatinine) During the Treatment Period
Time frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Change From Baseline in Serum Biochemistry (Calcium, Chloride, Magnesium, Potassium, Phosphate, Sodium, Urea) During the Treatment Period
Time frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Change From Baseline in Serum Biochemistry (Platelets, Leukocytes, Lymphocytes, Neutrophils, Monocytes, Eosinophils, Basophils) During the Treatment Period
Time frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Change From Baseline in Serum Biochemistry (Erythrocytes) During the Treatment Period
Time frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Changes From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period
Time frame: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Changes From Baseline in Respiratory Rate During the Treatment Period
Time frame: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Changes From Baseline in Heart Rate During the Treatment Period
Time frame: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Changes From Baseline in Weight During the Treatment Period
Time frame: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Number of Subjects With Physical Examination During the Treatment Period
Time frame: From start of study treatment to 6 weeks after study treatment (i.e., maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
Any physical examination finding that was classified by the investigator as a clinically significant change (compared with previous examination) was considered an AE, documented on the eCRF, and followed until the outcome was known. The below physical examination findings were recorded and reported. GDASC = General disorders and administration site conditions MND = Metabolism and nutrition disorders SSTD= Skin and subcutaneous tissue disorders MCTD = Musculoskeletal and connective tissue disorders IPPC = Injury, poisoning and procedural complications RTMD = Respiratory, thoracic and mediastinal disorders NBMU = Neoplasms benign, malignant and unspecified (include cysts and polyps) In the below table.
Number of Subjects With Signs of Long-Term Radiation Toxicity
Time frame: From start of study treatment upto 12 months
Long-term radiation toxicity included incidence of potential late toxicity, such as new primary cancers and bone marrow changes (acute myelogenous leukemia, myelodysplastic syndrome, and aplastic anemia).

Results and safety

Results posted to the registry on 9 Nov 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation	7	6
Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	3	3
Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	7	5
Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort	36	23
Docetaxel 75 mg/m^2 - Safety Cohort	17	9

Primary outcome: Number of Subjects With Dose-Limiting Toxicities - Dose Escalation Part

Time frame: From randomization until 6 weeks post-injection in all dose cohort of dose-escalation part. Number. Unit: Participants

Measure	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation n = 7	Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation n = 3	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation n = 7
Value	0	0	0

Primary outcome: Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Treatment-Emergent Serious Adverse Events (TESAE) With a CTCAE Grade of 3 or 4

Time frame: From start of study treatment to 6 weeks after study treatment (that is maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort) and 8 weeks for serious AEs. Number. Unit: Participants

Measure	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation n = 7	Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation n = 3	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation n = 7	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort n = 33	Docetaxel 75 mg/m^2 - Safety Cohort n = 13
TEAE CTCAE Grade 3	3	1	4	6	3
TEAE CTCAE Grade 4	2	1	1	10	6
TESAE	4	0	2	7	4

Population analysed: Only participants who received treatment were assessed

Primary outcome: Change From Baseline in Serum Biochemistry (Albumin, Protein, Hemoglobin) During the Treatment Period

Time frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort). Mean (Standard Deviation). Unit: gram per liter (G/L)

Measure	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation n = 7	Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation n = 3	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation n = 7	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort n = 35	Docetaxel 75 mg/m^2 - Safety Cohort n = 13
Albumin Baseline (n= 7,3,7,35,13)	42 (3)	43 (4)	43 (3.56)	42.7 (3.25)	42.3 (4.09)
Albumin: Change at Day 106 (n=1,0,0,27,11)	-2 (NA)	NA (NA)	NA (NA)	-1.3 (2.98)	-1.2 (2.75)
Albumin: Change at Day 190 (n= 0,0,0,24,6)	NA (NA)	NA (NA)	NA (NA)	-2.3 (3.33)	-0.5 (2.07)
Protein: Baseline (n= 7,3,7,35,13)	70.3 (4.23)	69.7 (8.5)	70.4 (4.89)	68.7 (4.45)	69.1 (5.33)
Protein: Change at Day 106 (n=1,0,0,27,11 )	1 (NA)	NA (NA)	NA (NA)	-3.9 (3.79)	-3.8 (2.56)
Protein: Change at Day 190 (n= 0,0,0,24,6)	NA (NA)	NA (NA)	NA (NA)	-5.3 (3.63)	-3.7 (4.18)
Hemoglobin: Baseline (n= 7,3,7,35,13)	122.43 (14.581)	120.67 (16.166)	120.43 (8.522)	122.82 (10.939)	120.23 (12.05)
Hemoglobin: Change at Day 106 (n=1,0,0,27,11 )	-10 (NA)	NA (NA)	NA (NA)	-8.81 (8.2)	-14.27 (9.067)

Population analysed: Only randomized participants who have this outcome measure tested were assessed

Primary outcome: Change From Baseline in Serum Biochemistry (Alkaline Phosphatase [AP], Alanine Aminotransferase [AAT], Lactate Dehydrogenase [LD]) During the Treatment Period

Time frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort). Mean (Standard Deviation). Unit: units per liter (U/L)

Measure	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation n = 7	Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation n = 3	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation n = 7	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort n = 33	Docetaxel 75 mg/m^2 - Safety Cohort n = 17
AP: Baseline (n= 7,3,7,33,13)	533.1 (656.36)	144 (89.2)	224.6 (115.08)	218.2 (207.63)	195.9 (110.86)
AP: Change at Day 106 (n=1,0,0,27,11)	-134 (NA)	NA (NA)	NA (NA)	-119.6 (153.1)	-78.9 (46.35)
AP: Change at Day 190 (n= 0,0,0,24,6)	NA (NA)	NA (NA)	NA (NA)	-119.3 (112.21)	-116.8 (52.21)
AAT: Baseline (n= 7,3,7,33,13)	17.6 (5.68)	17 (6.56)	18.9 (5.9)	19.8 (9.82)	19.8 (10.78)
AAT: Change at Day 106 (n=1,0,0,27,11 )	100 (NA)	NA (NA)	NA (NA)	2.9 (13.54)	-2.2 (11.75)
AAT: Change at Day 190 (n= 0,0,0,24,6)	NA (NA)	NA (NA)	NA (NA)	1.1 (8.67)	-3.7 (13.81)
LD: Baseline (n= 7,3,7,33,13)	313.3 (243.9)	179 (22.52)	214.4 (38.92)	212.8 (71.07)	203.4 (61.68)
LD: Change at Day 106 (n= 1,0,0,27,11)	15 (NA)	NA (NA)	NA (NA)	10.7 (58.14)	45.1 (93.58)

Population analysed: Only participants who received treatment were assessed

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation	4 of 7 (57.1%)	7 of 7 (100%)	Not reported
Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	0 of 3 (0%)	3 of 3 (100%)	Not reported
Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	2 of 7 (28.6%)	7 of 7 (100%)	Not reported
Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort	7 of 33 (21.2%)	33 of 33 (100%)	Not reported
Docetaxel 75 mg/m^2 - Safety Cohort	4 of 13 (30.8%)	13 of 13 (100%)	Not reported

Limitations and caveats (from the sponsor): The radium 223 dichloride treatment was calculated as 50 kBq per NIST 2010, and would be approximately 55 kBq per NIST 2015 standard. Pharmacokinetic endpoint was deleted as no PK variables were evaluated in the study.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31082669Morris MJ, Loriot Y, Sweeney CJ, Fizazi K, Ryan CJ, Shevrin DH, Antonarakis ES, Pandit-Taskar N, Deandreis D, Jacene HA, Vesselle H, Petrenciuc O, Lu C, Carrasquillo JA, Higano CS. Radium-223 in combination with docetaxel in patients with castration-resistant prostate cancer and bone metastases: a phase 1 dose escalation/randomised phase 2a trial. Eur J Cancer. 2019 Jun;114:107-116. doi: 10.1016/j.ejca.2019.04.007. Epub 2019 May 11.
Derived from this study: PubMed 26854432Gkialas IK, Fragkoulis C. Emerging therapies targeting castration-resistant prostate cancer. J BUON. 2015 Nov-Dec;20(6):1389-96.
Click here to find information about studies related to Bayer Healthcare products conducted in Europe.Link provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Bayer Study Director study director

Bayer

7 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Radium-223 dichloride (Xofigo, BAY88-8223) and Docetaxel in people with Bone Metastases and Castration-Resistant Prostate Cancer, run by Bayer at 7 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With Dose-Limiting Toxicities - Dose Escalation Part (time frame: From randomization until 6 weeks post-injection in all dose cohort of dose-escalation part). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01106352, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jan 2017.