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

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-02-03
• Last Update Posted: 5 November 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

Study & Design

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