E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic castration resistant prostate cancer (mCRPC) |
Etäpesäkkeitä lähettävä kastraatiohoitoon reagoimaton eturauhassyöpä |
|
E.1.1.1 | Medical condition in easily understood language |
Metastatic prostate cancer, which does not respond to hormonal treatment |
Etäpesäkkeitä lähettävä kastraatiohoitoon reagoimaton eturauhassyöpä |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036916 |
E.1.2 | Term | Prostate cancer stage D |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate safety and tolerability of ODM-204 including dose limiting
toxicities (DLTs) and the maximum tolerated dose (MTD), if possible |
|
E.2.2 | Secondary objectives of the trial |
To evaluate:
- PK profile of ODM-204 and its metabolites ORM-24178, ORM-25367, ORM-26343 and possible other metabolites after a single and repeated administration in fed and fasted condition at different dose levels
- PD profile of ODM-204 (including hormone and circulating tumour cell [CTC] measurements)
- preliminary antitumour activity of ODM-204 in different populations to be studied (see section 4.1) according to the following criteria:
PSA response; response in bone and soft tissue; time on treatment;
the dose of ODM-204 for further clinical studies; long term safety and tolerability of ODM-204; time to PSA and radiological progression |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent (IC) obtained.
2. Male aged ≥ 18 years.
3. Histologically or cytologically confirmed adenocarcinoma of prostate.
4. Castrate level of serum testosterone (< 1.7 nmol/l [50 ng/ml]) on GnRH agonist or antagonist therapy, or after bilateral orchiectomy. Patients who have not undergone bilateral orchiectomy must continue GnRH therapy during the study.
5. Metastatic disease documented by bone scan, CT or magnetic resonance imaging (MRI).
6. Prostate cancer progression documented by one or more of the following criteria:
PSA progression defined by a minimum of 2 rising PSA levels with an interval of at least 1 week between each determination. The PSA value at the screening visit should be ≥ 2 ng/ml.
- soft tissue disease progression as defined by RECIST 1.1 criteria
- bone disease progression defined by PCWG2 criteria (2 or more new lesions on bone scan compared with prior scan).
7. ECOG performance status 0-2.
8. Estimated life expectancy of at least 3 months.
9. Blood counts at screening:
- haemoglobin ≥ 10 g/dl
- absolute neutrophil count ≥ 1500/μl (1.5x10⁹/l)
- platelet count ≥ 100,000/μl (100x10⁹/l )
The subject must not have received any growth factor or blood transfusion within 7 days of the haematology laboratory values obtained at the screening visit.
10. Liver, renal and albumin values at screening:
- ALT and AST ≤ 2.5 x ULN
- total bilirubin ≤ 1.5 x ULN (except for subjects with a diagnosis of Gilbert’s disease)
- creatinine ≤ 1.5 x ULN
- albumin > 3.0 g/dl.
11. Serum potassium ≥ 3.5 mmol/l.
12. Able to swallow study treatments and comply with study requirements.
13. Acceptable and regular bowel movements in the judgement of the investigator without any acute, subacute or chronic gastrointestinal (GI) obstruction or other GI disorder or procedure which may interfere significantly with absorption of study treatment.
14. Sexually active subjects, unless surgically sterile, must agree to use condoms and an additional effective contraception method during the study treatment and for 3 months after the end of the study treatment.
15. Patients on systemic glucocorticoids for the treatment of prostate cancer or control of symptoms must have documented PSA progression by PCWG2 criteria prior start of study treatment. Patients with confirmed PSA progression while on systemic corticosteroids
other than Prednison® are required to switch to Prednison® 5 mg (once or twice a day depending on the previous glucocorticoid dose) prior the start of study treatment, but PSA progression does not have to be reconfirmed. |
|
E.4 | Principal exclusion criteria |
1. History of pituitary or adrenal dysfunction.
2. Known brain metastases.
3. Active infection or other medical condition that would make prednisone (corticosteroid) contraindicated.
4. Poorly controlled diabetes as judged by the investigator.
5. Prior therapy with any investigational CYP17A1i (e.g. TAK-700, TOK-001) or any investigational second-generation AR inhibitors (e.g. ARN-509, ODM-201).
6. Depending upon patient’s prior treatment, the following apply:
- prior chemotherapy: not more than 2 prior chemotherapy treatments are allowed; chemotherapy is not allowed within 4 weeks before the start of the study treatment
- prior abiraterone therapy must have been stopped at minimum 2 weeks before the start of the study treatment
- prior second-generation AR inhibitor therapy must have been stopped at minimum 4 weeks before the start of the study treatment.
7. Use of first-generation AR inhibitor within 4 weeks (within 6 weeks for bicalutamide and nilutamide) before start of the study treatment.
8. Systemic therapy with ketoconazole, or any other azole drug (e.g. fluconazole, itraconazole) within 4 weeks before the start of the study treatment.
9. Use of estrogens, cyproterone acetate, 5-α reductase inhibitors (finasteride, dutasteride) or biologic treatment within 4 weeks before the start of the study treatment. Prior radiotherapy within 4 weeks or palliative radiotherapy within 2 weeks before start of study treatment.
10. Any acute toxicities due to prior chemotherapy and/or radiotherapy that have not resolved to a NCI CTCAE (version 4.03) grade of ≤ 1. Chemotherapy induced alopecia and grade 2 peripheral neuropathy is allowed.
11. Initiation of an osteoclast-targeted therapy (bisphosphonate or denosumab) within 4 weeks before the start of the study treatment. Patients on a stable dose of osteoclast-targeted therapy for at least 4 weeks before the start of the study treatment can continue the
treatment during the study.
12. Participation in another interventional clinical trial and any concurrent treatment with any other investigational drug except those mentioned in exclusion criterion 7 within 4 weeks before start of the study treatment.
13. Uncontrolled hypertension
systolic BP ≥ 160 mmHg or
diastolic BP ≥ 95 mmHg.
Subjects with history of hypertension can be included, provided that BP is controlled by
anti-hypertensive therapy.
14. Clinically significant heart disease as judged by the investigator, e.g. congestive heart
failure New York Heart Association (NYHA) class ≥ 3, myocardial infarction, arterial
thrombotic and embolic events in the past 6 months, or unstable angina.
15. Prolonged QTc interval as evidenced by:
history or family history of long QTc syndrome
prolonged QT interval corrected by the Fridericia correction formula (QTcF) > 450 ms
on the centrally-read ECG at screening (2 of the measurements at screening > 450 ms).
16. Major surgery within 4 weeks before the start of the study treatment.
17. History of significant bleeding disorder unrelated to cancer, including:
diagnosed congenital bleeding disorders (e.g. von Willebrand’s disease)
diagnosed acquired bleeding disorder (e.g. acquired anti-factor VIII antibodies) within
1 year of screening visit
history of GI bleeding within 6 months of the screening visit.
18. Severe or uncontrolled concurrent medical condition or psychiatric illness.
19. Serious persistent infection within 2 weeks before the start of the study treatment.
20. Known history of hepatitis B, or hepatitis C.
21. Known hypersensitivity to the prednisone or study treatment or any of its ingredients (see
section 5.1).
22. Concomitant use of prohibited CYP substrates (see Appendix 4, column “Prohibited”). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Achieving a maximum tolerated dose (MTD) or dose limiting toxicity (DLT).
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
MTD is the dose level at which 2 or more out of 6 subjects in a cohort experience a DLT and those subjects who have received study treatment for 28 days or who had to discontinue study treatment earlier than 28 days because of DLT.
DLT is defined as any of the following toxicities with grade:
- ≥ 3 toxicity, excluding haematological toxicities, nausea, vomiting and diarrhoea
- ≥ 3 nausea, vomiting and diarrhoea uncontrolled with antiemetic and/or antidiarrheal therapy
- ≥ 3 haematological toxicity lasting for ≥ 7 days
- ≥ 4 thrombocytopenia and neutropenia
- Other laboratory values of ≥ grade 3 which are judged clinically significant by the investigator
- any other toxicity which in the judgement of the investigator and/or sponsor is viewed as a DLT.
|
|
E.5.2 | Secondary end point(s) |
PK profile; hormone assessment and circulating tumour cells (CTC).
For preliminary antitumour activity a serum total PSA concentration (PSA response and progression) and soft tissue response and progression will be evaluated (chest, abdomen and pelvic CT or MRI will be performed); bone response and progression will be evaluated by a radionuclide bone scan.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Serum total PSA concentration will be determined every 4 weeks until 24 weeks and every 12 weeks thereafter. In case of PSA progression a confirmatory test should be obtained 3-4 weeks later.
- Chest, abdomen and pelvic CT or MRI will be performed at screening, week 12 and every 12 weeks thereafter.
- Radionuclide bone scan will be performed at screening, week 12 and every 12 weeks thereafter, except for subjects with no bone metastasis or bone pain at week 12 the scan should be performed every 24 weeks. In case of bone progression, a confirmatory scan should be
performed in 6 weeks.
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
End-of-study visit will take place 28 days after the last study treatment dose with ± 4 days visit window. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |