Phase I/II, multi-center, open label study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of ASP9521 in patients with metastatic castrate-resistant prostate cancer
- Conditions
- Prostate cancerprostate carcinoma1002765510036958
- Registration Number
- NL-OMON38103
- Lead Sponsor
- Astellas Pharma
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 20
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 bisphosphonate 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 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. Antiandrogen 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 administered at least 4 weeks prior to screening.
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.
* Treatment with estramustine.
* Bicalutamide or nilutamide within 6 weeks prior to day of first dose of ASP9521.
* 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 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 ECG and clinical la
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Efficacy Variables:<br /><br>•The proportion of patients with a decline from baseline in PSA blood<br /><br>concentrations of >=50% after 12 weeks of once daily dosing with ASP9521.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Efficacy Variables<br /><br>• RECIST objective response rate.<br /><br>• Overall survival (OS).<br /><br>• Progression-free survival (PFS).<br /><br>• Time to clinical progression (TCP).<br /><br>• Time to PSA progression (TPP).<br /><br>• Time to radiographic progression (TRP).<br /><br>• CTC counts and CTC conversion rates.</p><br>