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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01106352
First received: April 16, 2010
Last updated: September 20, 2016
Last verified: September 2016

April 16, 2010
September 20, 2016
July 2010
June 2015   (final data collection date for 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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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).
  • Dose-escalation: Assessment of dose-limiting toxicities [ Time Frame: When 6 weeks post-injection data are available for the first combined injection of Alpharadin/docetaxel ] [ Designated as safety issue: Yes ]
  • Expanded safety cohort: Safety of combining Alpharadin with docetaxel (incidence and severity of adverse events and serious adverse events, changes from baseline in laboratory variables, vital signs and physical examination) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01106352 on ClinicalTrials.gov Archive Site
Not Provided
  • Signs of long-term radiation toxicity: incidence of manifestations of potential late toxicity, such as new primary cancers and bone marrow changes (acute myelogenous leukaemia, myelodysplastic syndrome, and aplastic anaemia) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Exploratory efficacy measurements of Alpharadin in combination with docetaxel versus docetaxel alone such as changes in bone markers, PSA and CTC, time to progression and overall survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Exploratory patient self-reporting of pain intensity [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Exploratory Efficacy: Weighted Mean Area Under the Curve for Bone Turnover Biomarkers [ Time Frame: From start of study treatment to 6 weeks after study treatment (maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort) ] [ Designated as safety issue: No ]
    Weighted mean area under the curve for the below bone turnover biomarkers were evaluated, ICTP = pyridinoline cross-linked carboxyterminal telopeptide P1NP = N-terminal peptide of procollagen type 1 uCTX-1 = urine C-telopeptide 1
  • Exploratory Efficacy: Time to Prostate-specific Antigen (PSA) Progression [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Serum PSA progression defined as two consecutive increases in PSA over a previous reference value within 6 months of first study treatment, each measurement at least 1 week apart.
  • Exploratory Efficacy: Percent Change From Baseline in Circulating Tumor Cells at Day 85 [ Time Frame: Baseline, Day 85, expanded safety cohort ] [ Designated as safety issue: No ]
    CTCs were measured to follow the evolution of the level of CTCs after treatment.
  • Exploratory Efficacy: Time to Clinical or Radiographic Progression [ Time Frame: From start of study treatment to 12 months, at every 12 weeks ] [ Designated as safety issue: No ]

    Time to first radiologic or clinical progression is determined by one of the following:

    • For soft tissue lesions, the determination is based on Response Evaluation Criteria in Solid Tumors 1.1.
    • For bone disease, the determination is based on Prostate Cancer Working Cohort 2 (PCWG2) definitions, which require the appearance of at least 2 new lesions with a confirmatory bone scan at least 6 or more weeks later. For clinical progression, the investigators followed the recommendations of the PCWG25 and used their clinical judgment to determine clinical progression.
  • Progression Free Survival (PFS) End Point [ Time Frame: From start of study treatment to 12 months, at every 12 weeks ] [ Designated as safety issue: No ]
    PFS defined as the time from randomization (randomization referred to the date of treatment assignment) to disease progression (radiological or clinical, whichever was earlier) or death (if death occurred before progression was documented). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation.
  • Overall Survival Rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The overall survival (OS) time in days was calculated as number of days since the day of first dose of study medication until the date of death.
  • Number of Subjects Who Responded to Interactive Voice Response System (IVRS) Pain [ Time Frame: From start of study treatment until 12 months ] [ Designated as safety issue: No ]
    The subject completed the full BPI (short form) paper questionnaire, and clinical staff completed the analgesic log. The test consists of 10 questions addressing severity, location, chronicity, and amount of relief. In question 3, subjects with pain are asked to evaluate the severity of pain at worst in the past 24 hours in a 0 to 10 scale, with 0 indicating no pain, and 10 indicating the worst pain.
Not Provided
 
A Study of Alpharadin With Docetaxel in Patients With Bone Metastasis From Castration-Resistant Prostate Cancer (CRPC)
A Phase I/IIa Study of Safety and Efficacy of Alpharadin® With Docetaxel in Patients With Bone Metastasis From Castration-Resistant Prostate Cancer
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.
The trial was initially conducted and submitted by Algeta ASA. After acquiring Algeta, Bayer is now the sponsor.
Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Bone Metastases
  • Castration-Resistant Prostate Cancer
  • Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
    Alpharadin (Radium-223 dichloride) is administered intravenously as a bolus injection.
  • Drug: Docetaxel
    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.
  • Experimental: Radium-223 dichloride (Xofigo, BAY88-8223) + docetaxel
    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.
    Interventions:
    • Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
    • Drug: Docetaxel
  • Active Comparator: Docetaxel
    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.
    Intervention: Drug: Docetaxel
Gkialas IK, Fragkoulis C. Emerging therapies targeting castration-resistant prostate cancer. J BUON. 2015 Nov-Dec;20(6):1389-96. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
70
June 2015
June 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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.
  • 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
Male
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   France
 
NCT01106352
15469, BC1-10, 2011-000822-31
No
Not Provided
Not Provided
Bayer
Bayer
Not Provided
Study Director: Bayer Study Director Bayer
Bayer
September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP