SAFETY, ABSORPTION AND DISTRIBUTION OF ODM-201 IN PATIENTS WITH PROSTATE CANCER:

• Register: EUCTR
• Last refreshed on: 19 August 2013
• Main ID: EUCTR2010-022802-41-EE
• Date of registration: 05/12/2012
• Prospective Registration: Yes
• Primary sponsor: Orion Corporation Orion Pharma
• Public title: SAFETY, ABSORPTION AND DISTRIBUTION OF ODM-201 IN PATIENTS WITH PROSTATE CANCER:
• Scientific title: SAFETY AND PHARMACOKINETICS OF ODM-201 IN PATIENTS WITH CASTRATE RESISTANT PROSTATE CANCER: OPEN, NON-RANDOMISED, UNCONTROLLED, MULTICENTRE, MULTIPLE DOSE ESCALATION STUDY WITH A RANDOMISED PHASE II EXPANSION COMPONENT - Arades Phase I/II
• Date of first enrolment: 28/12/2012
• Target sample size: 130
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022802-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Czech Republic, Estonia, Finland, France, Sweden, United Kingdom, United States

Contacts

• Name: Virpi Mononen
• Affiliation: Orion Corporation Orion Pharma

• Name: Virpi Mononen
• Affiliation: Orion Corporation Orion Pharma

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent (IC) obtained.
2.Male patients aged 18 years or older.
3.Histologically confirmed adenocarcinoma of prostate.
4.Ongoing androgen deprivation therapy with a LHRH analogue or antagonist or bilateral orchiectomy and serum testosterone level < 50 ng/dl (< 0.5 ng/ml, < 1.7 nmol/l) at screening.
5.Progressive metastatic disease during the androgen deprivation, and after the treatment with antiandrogen and antiandrogen withdrawal, demonstrated by 1 or more of the following criteria:
•patients with measurable or non-measurable disease (i.e. no target lesions), progression defined by a new soft tissue lesion or rising PSA value over 2 ng/ml in at least 2 rising successive measurements, at least 1 week apart. If the confirmatory PSA value is less than the screening PSA value, then an additional test for the rising PSA is required to document progression.
•patients with measurable disease, progression defined by RECIST 1.1 criteria.
•patients with metastatic bone disease, progression defined by 2 or more new lesions in a radionuclide bone scan.
6.The patient:
•has received 1 or 2 chemotherapy treatments, or
•is ineligible for chemotherapy, or
•is intolerant of chemotherapy, or
•has declined chemotherapy, or
•has no need for chemotherapy yet.
7.The patient has ECOG performance status of 0-1 at screening.
8.The patient has at screening blood counts:
•absolute neutrophil count = 1.5 x 109/l),
•thrombocytes = 100 x 109/l),
•haemoglobin = 10 g/dl (can be post-transfusion).
9.The patient has at screening liver, renal and albumin values of:
•alanine aminotransferase (ALT) or aspartate transaminase (AST) = 2.5 x upper limit of normal (ULN),
•total bilirubin = 2 x ULN,
•creatinine = 1.5 x ULN,
•albumin > 3.0 g/dl
10.Prior treatment with antiandrogen. Discontinuation of bicalutamide or nilutamide at least 6 weeks and other antiandrogens at least 4 weeks prior to the start of the study treatment.
11.Life expectancy of at least 3 months.
12.Sexually active patients must agree to use condoms as an effective barrier method during the study treatment and for 3 months after the end of the treatment
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 65
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 65

Exclusion criteria:
1.Known hypersensitivity to the study treatment formulation excipients.
2.The patient has received prior therapy with MDV3100 or any investigational AR antagonist.
3.The patient has received chemotherapy, radiotherapy or any experimental therapy within 4 weeks (within 6 weeks for nitrosoureas and mitomycin C) of the start of the study treatment or has not recovered to grade = 1 or returned to baseline from any acute treatment-related toxicities of the previous therapy except for alopecia and grade 2 neuropathy.
4.Initiation of bisphosphonate therapy within 4 weeks prior to the start of the study treatment. Patients on a stable dose of bisphosphonate for at least for 30 days prior to the start of the study treatment can continue the treatment during the study.
5.Therapy with estrogen within 30 days prior the start of the study treatment. 6.Therapy with oral ketoconazole or CYP17 inhibitor within 30 days prior to the start of the study treatment.
7.Use of systemic corticosteroid with dose greater than the equivalent of 10 mg of prednisone/day within 30 days prior to the start of the study treatment. Patients on a stable maintenance dose of corticosteroid = 10 mg/day can continue the treatment during the study.
8.Prior use of any herbal products known to decrease PSA levels (e.g. PC-SPES or saw palmetto) within 30 days prior the start of the study treatment.
9.Known metastases in the brain.
10.History of other malignancy within the previous 5 years, except a basal cell carcinoma of skin.
11.Major surgery within 4 weeks prior to the start of the study treatment. 12.Serious persistent infection within 14 days prior to the start of the study treatment.
13.Known gastrointestinal disease or procedure that affects the absorption of the study treatment.
14.Serious concurrent medical condition or psychiatric illness.
15.History of congestive heart failure New York heart association (NYHA) class III or IV or uncontrolled hypertension at screening.
16.History or family history of long QTc syndrome.
17.Abnormalities in centrally read 12-lead ECG considered by the investigator to be clinically significant or PR interval > 200 ms or prolongation or shortening of the rate-corrected (Fridericia) QT interval (repeated demonstration of QTc interval > 450 ms or < 300 ms) at screening.
18.The patient has received any investigational treatment within 30 days prior to the start of the study treatment.
19.Known history of hepatitis B, or hepatitis C.
20.Any condition that, in the opinion of the investigator, would impair the patient's ability to comply with study procedures.
21.The patient is not able to swallow the study treatment capsules.


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

Health Condition(s) or Problem(s) studied

Progressive castration resistant prostate cancer (MedDRA: hormone-refractory prostate cancer)
MedDRA version: 14.1 Level: LLT Classification code 10062904 Term: Hormone-refractory prostate cancer System Organ Class: 100000004864

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

Intervention(s)

Product Name: ODM-201
Product Code: ODM-201
Pharmaceutical Form: Capsule
INN or Proposed INN: .
Current Sponsor code: ODM-201
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Secondary Objective: To evaluate PK profile of ODM-201 (by using the sum of diastereomers concentrations) and its major metabolite after single and multiple dose administartions in fed condition at different dose level. Preliminary antitumor activity of ODM-201 will be evaluated by PSA, soft tissue and bone lesions, circulating tumor cell (CTC) counts, ECOG performance status, and by the time on treatment. As well as to evaluate the effects of ODM-201 on concentration of serum bone markers.

Main Objective: To evaluate safety and tolerability of ODM-201 and to define dose(s) of ODM-201 for further clinical studies. Dose-limiting toxicities (DLT) and the MTD and/or OTD will be determined.

Primary end point(s): To establish a dose limiting toxicity or maximum tolerated dose (MTD), if possible, by assessing the adverse events using the NCI CTCAE version 4.03.

Timepoint(s) of evaluation of this end point: DLT (and MTD if possible) at 28 days time point in each cohort. Safety-tolerability at the end of the study at 12 weeks timepoint

Secondary Outcome(s)

Secondary end point(s): To evaluate PK profile after single and multiple dose administrations in fed condition at different dose levels.
Preliminary antitumour activity will be evaluated by PSA, soft tissue and bone
lesions, CTC counts, ECOG performance status, and by the time on treatment.
The dose(s) of ODM-201 for further clinical studies will be defined.

Timepoint(s) of evaluation of this end point: PK. Phase 1: Days 1, 7, 14, 21, 28; Phase 2: day 28 and week 12.
Phase 1 & phase 2: PSA, soft tissue and bone lesions, CTC counts, ECOG performance status at 12 weeks timepoint.
Phase 2: additionally AR gene mutations from CTC at day 1

Secondary ID(s)

3104001

2010-022802-41-GB

Source(s) of Monetary Support

Orion Corporation Orion Pharma