A Randomized, Double-Blind, Phase II, Efficacy and Safety Study of MDV3100 (ASP9785) vs. Bicalutamide in Castrate Men with Metastatic Prostate Cancer - Terrain

• Register: EUCTR
• Last refreshed on: 11 December 2017
• Main ID: EUCTR2010-021868-15-DK
• Date of registration: 15/05/2012
• Prospective Registration: Yes
• Primary sponsor: Astellas Pharma Global Development, Inc. (APGD)
• Public title: A Randomized, Double-Blind, Phase II, Efficacy and Safety Study of MDV3100 (ASP9785) vs. Bicalutamide in Castrate Men with Metastatic Prostate Cancer - Terrain
• Scientific title: A Randomized, Double-Blind, Phase II, Efficacy and Safety Study of MDV3100 (ASP9785) vs. Bicalutamide in Castrate Men with Metastatic Prostate Cancer - Terrain
• Date of first enrolment: 22/05/2012
• Target sample size: 370
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-021868-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, Denmark, Germany, United Kingdom, United States

Contacts

• Name: Teresa Sheehan, Clin. Study Manager
• Affiliation: Astellas Pharma Global Development, Inc. (APGD)

• Name: Teresa Sheehan, Clin. Study Manager
• Affiliation: Astellas Pharma Global Development, Inc. (APGD)

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion Criteria for Double Blind Period
1. IRB/IEC approved written Informed Consent and privacy language as per national
regulations (e.g., HIPAA for U.S. sites) must be obtained from the subject prior to any
study-related procedures (including withdrawal of prohibited medication, if applicable).
2. Histologically confirmed adenocarcinoma of the prostate without neuroendocrine
differentiation or small cell features.
3. Ongoing androgen deprivation therapy with a LHRH agonist or antagonist at a stable dose
and schedule within 4 weeks of randomization or bilateral orchiectomy (i.e., surgical or
medical castration).
4. Serum testosterone level = 1.7 nmol/L (50 ng/dL) at Screening.
5. Metastatic disease documented on or before screening visit by one of the following:
? At least two bone lesions on bone scan, or
? Soft tissue disease documented by CT/MRI, or
? Unequivocal pelvic adenopathy short axis > 2.0 cm in diameter by CT/MRI.
6. Progressive disease at study entry defined as one or more of the following three criteria
occurring in the setting of castrate levels of testosterone:
? PSA progression defined by a minimum of three rising PSA levels with an
interval of = 1 week between each determination. The PSA value at the Screening
visit should be = 2 µg/L (2 ng/mL);
? Soft tissue disease progression defined by RECIST 1.1.;
? Bone disease progression defined by two or more new lesions on bone scan.
7. Asymptomatic or mildly symptomatic from prostate cancer (i.e. the score on BPI-SF
Question #3 must be < 4); no use of opiate analgesics for prostate cancer-related pain
currently or anytime within 4 weeks prior to randomization.
8. ECOG performance status of 0-1, including subjects with decreased performance status not
attributed to progressive and symptomatic prostate cancer.
9. Estimated life expectancy of = 12 months.
10. Able to swallow the study drug and comply with study requirements.
Inclusion Criteria for Open Label Period:
Subjects must meet the following inclusion criteria:
1. IRB/IEC approved written Informed Consent and privacy language as per national regulations (e.g., HIPAA for U.S. sites) must be obtained from the subject prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
2. Received double-blind study treatment during the study. If treated with enzalutamide during double-blind period, treatment must be ongoing at time of Open Label enrollment.
3. Ongoing androgen deprivation therapy with a LHRH agonist or antagonist at a stable dose and schedule unless already had a bilateral orchiectomy.
4. Able to swallow the study drug and comply with study requirements.
5. A male subject and his female spouse/partner who is of childbearing potential must continue to use two acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) throughout the Open-Label Period, and for 3 months after final study drug administration. Two acceptable forms of birth control include:
1. Condom (barrier method of contraception), AND
2. In addition to a condom, one of the following acceptable forms of contraception is required:
•Established use of oral, injected or implanted hormonal methods of contraception.
•Placement of an intrauterine device (IUD) or intrauterine system (IUS).
•Barrier methods of contraception: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/supposit
Exclusion criteria:
Exclusion Criteria for Double Blind Period
Prior cytotoxic chemotherapy for prostate cancer.
Severe concurrent disease, infection, or comorbidity that, in the judgment of the investigator, would make the subject inappropriate for enrollment.
Known or suspected brain and/or skull metastasis or active epidural disease.
History of another malignancy within the previous 5 years other than curatively treated nonmelanomatous skin cancer.
Current or prior treatment with estrogens and/or drugs with anti-androgenic properties such as spironolactone > 50 mg/kg, or progestational agents for the treatment of prostate cancer within 6 months prior to randomization.
Current or prior use of ketoconazole for the treatment of prostate cancer.
Use of antiandrogens within 6 weeks prior to randomization.
Documented prior disease progression while receiving antiandrogens. Disease progression defined as PSA progression, radiographic progression and/or clinical deterioration.
Current or prior treatment with 5-a reductase inhibitors or anabolic steroids within 6 months prior to randomization.
Prior use of systemic glucocorticoids (the equivalent of 10 mg of prednisone) within 3 months prior to randomization or expectation of their use during the study.
Radiation therapy to bone lesions or prostatic bed within 4 weeks prior to randomization.
Major surgery within 2 months prior to randomization.
History of seizure including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization). Also, current or prior treatment with anti-epileptic medications for the treatment of seizures or history of loss of consciousness or transient ischemic attack within 12 months prior to randomization.
Clinically significant cardiovascular disease including Myocardial infarction within past six months or uncontrolled angina within past three months.
Exclusion Criteria for Open Label Period:
NOTE: The exclusion criteria apply only to subjects starting treatment with enzalutamide after receiving bicalutamide in the double-blind period.
Subjects must not meet any of the following exclusion criteria:
1.Has taken commercially available enzalutamide (Xtandi);
2.Severe concurrent disease, infection, or comorbidity that, in the judgment of the investigator, would make the subject inappropriate for enrollment;
3.Has current or previously treated brain metastasis or active leptomeningeal disease;
4.Has a history of seizure or a condition that may increase the risk of seizure;
5.Has any of the following: total bilirubin = 1.5 times the ULN (except patients with a diagnosis of Gilbert’s disease), ALT or AST = 2.5 times ULN at enrollment into open-label period. For patients with documented liver metastases, ALT and AST exclusion is > 5 times ULN;
6.Has creatinine > 2 mg/dL (177 µmol/L) at enrollment into Open-label period.
7.Met one or more discontinuation criteria in the double-blind period >30 days prior to enrollment in Open-Label Period.
8.Use of another anti androgen, cytotoxic chemotherapy or other investigational drug within 4 weeks prior to Open-Label enrollment.



Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Metastatic Prostate Cancer
MedDRA version: 19.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: MDV3100
Product Code: MDV3100
Pharmaceutical Form: Capsule, soft
CAS Number: 915087-33-1
Current Sponsor code: MDV3100
Other descriptive name: 3-(4-cyano-3-trifluoromethylphenyl)- 1-[3-fluoro-4-(methylcarbamoyl)phenyl]-5,5-dimethyl -2-thioxoimidazolin-4-one
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pharmaceutical form of the placebo: Capsule, soft
Route of administration of the placebo: Oral use

Trade Name: Bicalutamide Tablets, USP

Product Name: Bicalutamide
Pharmaceutical Form: Tablet
INN or Proposed INN: BICALUTAMIDE
CAS Number: 90357065
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: The duration of progression-free survival (PFS) will be calculated from the date of randomization to the date of first objective evidence of radiographic disease progression, skeletal-related event, initiation of new anti-neoplastic therapy, or death by any cause, whichever occurs first. Subjects must be assessed with CT/MRI and bone scan within 28 days prior to randomization (Day 1). Scans should be scheduled in such a way that the scan results are available at the regularly scheduled visits at week 13, 25 and every subsequent 12 weeks.

Secondary Objective: To determine the safety of treatment with MDV3100 as compared to bicalutamide;
To determine the PSA response of MDV3100 at week 13 as compared to bicalutamide;
To determine the time to PSA progression of MDV3100 as compared to bicalutamide.

Main Objective: To determine the PFS of MDV3100 as compared to bicalutamide

Primary end point(s): Progression-free survival

Secondary Outcome(s)

Secondary end point(s): 1)To determine the safety of treatment with MDV3100 as compared to bicalutamide
2)To determine the prostate specific antigen (PSA) response of MDV3100 at week 13 as compared to bicalutamide
3)To determine the time to PSA progression of MDV3100 as compared to bicalutamide

Timepoint(s) of evaluation of this end point: 1) at avery visit
2) at week 13
3) week, 13, 25 and every subsequent 12 weeks, 30 days from date of last dose, 60 days from date of last dose, Every 12 weeks from date of last dose

Secondary ID(s)

74,563

2010-021868-15-GB

9785-CL-0222

Source(s) of Monetary Support

Astellas Pharma Global Development, Inc. (APGD)