Clinical trial NCT01106352: A Study of Alpharadin With Docetaxel in Patients With Bone Metastasis From Castration-Resistant Prostate Cancer (CRPC)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2010-04-19
Enrollment: 70
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of Subjects With Dose-Limiting Toxicities - Dose Escalation Part
timeFrame: From randomization until 6 weeks post-injection in all dose cohort of dose-escalation part
measure: Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Treatment-Emergent Serious Adverse Events (TESAE) With a CTCAE Grade of 3 or 4
timeFrame: 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
measure: Change From Baseline in Serum Biochemistry (Albumin, Protein, Hemoglobin) During the Treatment Period
timeFrame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
measure: Change From Baseline in Serum Biochemistry (Alkaline Phosphatase [AP], Alanine Aminotransferase [AAT], Lactate Dehydrogenase [LD]) During the Treatment Period
timeFrame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
measure: Change From Baseline in Serum Biochemistry (Bilirubin, Creatinine) During the Treatment Period
timeFrame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
measure: Change From Baseline in Serum Biochemistry (Calcium, Chloride, Magnesium, Potassium, Phosphate, Sodium, Urea) During the Treatment Period
timeFrame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
measure: Change From Baseline in Serum Biochemistry (Platelets, Leukocytes, Lymphocytes, Neutrophils, Monocytes, Eosinophils, Basophils) During the Treatment Period
timeFrame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
measure: Change From Baseline in Serum Biochemistry (Erythrocytes) During the Treatment Period
timeFrame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
measure: Changes From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period
timeFrame: 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)
measure: Changes From Baseline in Respiratory Rate During the Treatment Period
timeFrame: 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)
measure: Changes From Baseline in Heart Rate During the Treatment Period
timeFrame: 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)
measure: Changes From Baseline in Weight During the Treatment Period
timeFrame: 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)
measure: Number of Subjects With Physical Examination During the Treatment Period
timeFrame: 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)
measure: Number of Subjects With Signs of Long-Term Radiation Toxicity
timeFrame: From start of study treatment upto 12 months
Secondary outcomes:
Other outcomes:
measure: Exploratory Efficacy: Weighted Mean Area Under the Curve for Bone Turnover Biomarkers
timeFrame: From start of study treatment to 6 weeks after study treatment (maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
measure: Exploratory Efficacy: Time to Prostate-specific Antigen (PSA) Progression
timeFrame: 12 months
measure: Exploratory Efficacy: Percent Change From Baseline in Circulating Tumor Cells at Day 85
timeFrame: Baseline, Day 85, expanded safety cohort
measure: Exploratory Efficacy: Time to Clinical or Radiographic Progression
timeFrame: From start of study treatment to 12 months, at every 12 weeks
measure: Progression Free Survival (PFS) End Point
timeFrame: From start of study treatment to 12 months, at every 12 weeks
measure: Overall Survival Rate
timeFrame: 12 months
measure: Number of Subjects Who Responded to Interactive Voice Response System (IVRS) Pain
timeFrame: From start of study treatment until 12 months
Locations:
city: San Francisco
country: United States
state: California
city: Evanston
country: United States
state: Illinois
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: New York
country: United States
state: New York
city: Seattle
country: United States
state: Washington
city: Villejuif Cedex
country: France
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Gkialas IK, Fragkoulis C. Emerging therapies targeting castration-resistant prostate cancer. J BUON. 2015 Nov-Dec;20(6):1389-96.