Phase I/II Study of ASP9521 in Castrate-Resistant Prostate Cancer (CRPC) Patients

• Conditions: metastatic castrate-resistant prostate cancer; MedDRA version: 14.1Level: PTClassification code 10036911Term: Prostate cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-023382-22-NL
• Lead Sponsor: Astellas Pharma Europe B.V. (APEB)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-07-11
• Last Update Posted: 22 October 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 186

Inclusion Criteria

A patient is eligible for the study if all of the following apply:
1.Institutional Review Board (IRB) / Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations must be obtained from the patient or legally authorized representative prior to any study-related procedures.
2.Male aged 18 years or older. Female sexual partners of male participants in the study must be non-fertile, i.e., surgically sterilized or must practice an adequate contraceptive method to prevent pregnancies. Adequate contraceptive methods are defined as: sexual abstinence from the day of partner’s dosing until 3 months after the last dose; the use of a condom in addition to having their partner use another acceptable method (oral or injectable hormonal contraceptives, contraceptive patch, intra-uterine devices, vaginal hormonal rings, or sterilization by surgery, a vaginal diaphragm or cervical caps) during the study and for up to 3 months after the last dose; patient’s sexual partner is of non-child bearing potential i.e., post-menopausal, surgically sterilized (e.g., tubal ligation), or hysterectomy in medical history.
3.Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features.
4.Metastatic disease documented by 2 or more bone lesions on bone scan or by soft tissue disease observed by CT/MRI.
5.Ongoing androgen deprivation with LHRH agonist/antagonist therapy or bilateral orchiectomy. For patients who have not had an orchiectomy, there must be a plan to maintain effective LHRH agonist/antagonist therapy for the duration of the study.
6.Serum testosterone <1.7 nmol/L (50 ng/dL) at screening.
7.Patients receiving bisphosphonates or other approved bone targeting therapy must have been on stable doses for at least 4 weeks prior to screening.
8.Progressive disease at study entry defined as one or more of the following 3 criteria occurring in the setting of castrate levels of testosterone:
?PSA progression defined by a minimum of 2 rising PSA levels with an interval of >1 week between each determination. The PSA value at screening should be >2 ng/mL.
?Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST). Measurable disease is not required for entry. Lymph nodes >20 mm are considered measurable disease.
?Bone disease progression defined by at least 2 new lesions on bone scan.
9.Life expectancy of >6 months according to the investigator’s judgment.
The following inclusion criteria must be fulfilled by chemotherapy-naïve patients:
10.Eastern Cooperative Oncology Group (ECOG) scores of 0 to 1.
11.Asymptomatic or controlled symptomatic patients with metastatic CRPC who have failed one or more lines of hormonal treatment/androgen deprivation therapy but have not received chemotherapy or have refused chemotherapy.
12.No prior chemotherapy for prostate cancer.
13.Anti-androgen withdrawal patients receiving an anti androgen as part of primary androgen ablation must demonstrate disease progression following discontinuation of anti-androgen (>4 weeks since last flutamide dose or >6 weeks since last bicalutamide or nilutamide dose).
The following inclusion criteria must be fulfilled by post chemotherapy patients:
14.ECOG scores of 0 to 2.
15.No more than 2 prior regimens of chemotherapy for prostate cancer, of which one is docetaxel-based to have been received at least 4 weeks prior

Exclusion Criteria

Patients will be excluded from participation in the study if any of the following apply:
1.Concomitant treatment with the following is prohibited according to stratification as chemotherapy-naïve or post-chemotherapy patients:
?Chemotherapy-naïve patients:
?All chemotherapeutic agents.
?All biologic agents (except for sipuleucel T [Provenge®]), or other agents with anti-tumor activity against prostate cancer, including 5 alpha reductase inhibitors, androgens (e.g., testosterone), cytoproterone acetate and all other progestational agents, estrogens, and flutamide within 4 weeks prior to day of first dose of ASP9521.
?Bicalutamide or nilutamide within 6 weeks prior to day of first dose of ASP9521.
?Treatment with estramustine.
?Ketoconazole for treatment of prostate cancer.
?Treatment with abiraterone.
?Post-chemotherapy patients:
?All biologic agents (except for sipuleucel T [Provenge®]), or other agents with anti-tumor activity against prostate cancer, including 5 alpha reductase inhibitors, androgens (e.g., testosterone), progestational agents, estrogens, flutamide within 4 weeks prior to day of first dose of ASP9521.
?Bicalutamide or nilutamide within 6 weeks prior to day of first dose of ASP9521.
?Ketoconazole for treatment of prostate cancer.
?Treatment with abiraterone.
2.Use of herbal products that may have hormonal anti prostate cancer activity and/or are known to decrease PSA levels or Prednisolone > 10 mg (or an equivalent) for the treatment of prostate cancer within 4 weeks of day of first dose of ASP9521, or plans to initiate the above within the study period.
3.Radiation therapy for treatment of the prostate within 3 months prior to screening.
4.Radiation therapy for the treatment of metastases within 3 weeks (if single fraction of radiotherapy then within 2 weeks) and radionuclide therapy for the treatment of metastases within 4 weeks prior to screening.
5.Major surgery within 2 months prior to screening.
6.Known or suspected intracerebral disease or brain metastasis.
7.History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer.
8.Gastrointestinal disorder affecting absorption (e.g., gastrectomy or active peptic ulcer disease).
9.Any of the following significant ophthalmological abnormalities:
a.Abnormal intraocular pressure (IOP).
b.Abnormal fundus, like age-related macular degeneration (AMD) or other retinal damage
10.Significant cardiovascular disease including:
?Myocardial infarction within 6 months prior to screening.
?Uncontrolled angina within 3 months prior to screening.
?Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patients with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multigated acquisition scan (MUGA) performed within 3 months results in a left ventricular ejection fraction that is =45%.
?History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes).
?History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
?Uncontrolled hypertension as indicated by a resting systolic blood pressure (BP) >170 mmHg or diastolic BP >105 mmHg at screening.
11.Concurrent disease or any clinically significant abnormality following the investigator’s review of the pre-study physical examination, 12-lead

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified