Safety and Pharmacokinetics Study of ODM-201 in Castrate Resistant Prostate Cancer

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

The purpose of this study is to evaluate safety, tolerability and pharmacokinetics of ODM-201 in patients with castrate resistant prostate cancer.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: ODM-201

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Czech Republic
  • Hradec Králové, Czech Republic
    • Klinika onkologie a radioterapie LFUK a FN
  • Olomouc, Czech Republic
    • Fakultni Nemonicnice Olomouc
  • Znojmo, Czech Republic
    • Oddeleni Radiacni a Klinicke Onkologie Nemocnice Znojmo
• Estonia
  • Talinn, Estonia
    • East-Tallinn Central Hospital
• Finland
  • Helsinki, Finland
    • Helsinki University Central Hospital
  • Kuopio, Finland
    • Kuopio University Hospital
  • Oulu, Finland
    • Oulu University Hospital
  • Tampere, Finland
    • Tampere University Hospital
  • Turku, Finland
    • Turku University Hospital
• France
  • Paris, France
    • Saint Louis Hospital
  • Villejuif, France
    • Institut Gustave Roussy
• United Kingdom
  • Birmingham, United Kingdom
    • Queen Elizabeth Hospital
  • Cardiff, United Kingdom
    • Velindre Cancer Centre
  • Manchester, United Kingdom
    • Christie Hospital
  • Oxford, United Kingdom
    • Churchill Hospital
• United States
  • Colorado
    • Wheat Ridge, Colorado, United States, 80211
      • The Urology Center of Colorado
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Eastern CT Hematology and Oncology Associates
  • Florida
    • Ocala, Florida, United States, 34474
      • Urology Health Team PLLC
  • Maryland
    • Baltimore, Maryland, United States, 21327
      • Chesapeake Urology Research Associates
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Delaware Valley Urology, LLC
  • New York
    • Brooklyn, New York, United States, 11215
      • Brooklyn Urology Research Group
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Written informed consent
• Histologically confirmed adenocarcinoma of prostate
• Ongoing androgen deprivation therapy with a LHRH analogue or antagonist or bilateral orchiectomy
• Progressive metastatic disease
• Adequate bone marrow, hepatic, and renal function

Exclusion Criteria:

• Known metastases in the brain
• History of other malignancy within the previous 5 years
• Known gastrointestinal disease or procedure that affects the absorption
• Not able to swallow the study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ODM-201 Phase I	Drug: ODM-201; ODM-201 administered orally daily
Experimental: ODM-201 Phase II Dose 1	Drug: ODM-201; ODM-201 administered orally daily
Experimental: ODM-201 Phase II Dose 2	Drug: ODM-201; ODM-201 administered orally daily
Experimental: ODM-201 Phase II Dose 3	Drug: ODM-201; ODM-201 administered orally daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Number of Participants Who Experienced Dose Limiting Toxicity (DLT)	A DLT was any Grade 3 or more toxicity (by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE version 4.03]) excluding less than Grade 4 neutropenia or thrombocytopenia, hematological toxicity lasting less than 7 days, and nausea, vomiting, diarrhea controlled with antiemetic and/or anti-diarrheal treatment.	Up to 28 days for each cohort
Phase 1: Number of Dose Limiting Toxicities Used to Determine the Maximum Tolerated Dose	The MTD is defined as dose level at which 2 or more out of 6 participants experience a dose limiting toxicity (DLT)	Up to 28 days for each cohort

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 and 2: Participants With Decline of at Least 50% in Prostate-specific Antigen (PSA) in Chemotherapy-naïve and CYP17i-naïve Group	Number of participants with greater than or equal to 50% decrease in serum PSA from baseline at 12 weeks in group of participants who were naïve to both chemotherapy and CYP17 inhibitor	3 months
Phase 1 and 2: Participants With Decline of at Least 50% in Prostate-specific Antigen (PSA) in Post-chemotherapy and CYP17i-naïve Group	Number of participants with greater than or equal to 50% decrease in serum PSA from baseline at 12 weeks in group of participants previously treated with chemotherapy but not CYP17 inhibitor	3 months
Phase 1 and 2: Participants With Decline of at Least 50% in Prostate-specific Antigen (PSA) in Post-CYP17i Group	Number of participants with greater than or equal to 50% decrease in serum PSA from baseline at 12 weeks in group of participants previously treated with CYP17 inhibitor	3 months
Phase 1 and 2: Participants With RECIST Response in Soft Tissue in Chemotherapy-naïve and CYP17i-naïve Group	Number of participants with overall complete response (CR), partial response (PR) or stable (SD) soft tissue disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in chest, abdomen, and pelvic CT or MRI scans.	3 months
Phase 1 and 2: Participants With RECIST Response in Soft Tissue in Post-chemotherapy and CYP17i-naive Group	Number of participants with overall complete response (CR), partial response (PR) or stable (SD) soft tissue disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in chest, abdomen, and pelvic CT or MRI scans.	3 months
Phase 1 and 2: Participants With RECIST Responses in Soft Tissue in Post-CYP17i Group	Number of participants with overall complete response (CR), partial response (PR) or stable (SD) soft tissue disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in chest, abdomen, and pelvic CT or MRI scans.	3 months
Phase 1 and 2: Participants With Stable Bone Disease in Chemotherapy-naïve and CYP17i-naïve Group	Number of participants with stable bone disease (no change). Radiographic bone progression was defined by the appearance of two or more new lesions on bone scan	3 months
Phase 1 and 2: Participants With Stable Bone Disease in Post-chemotherapy and CYP17i-naïve Group	Number of participants with stable bone disease (no change). Radiographic bone progression was defined by the appearance of two or more new lesions on bone scan	3 months
Phase 1 and 2: Participants With Stable Bone Disease in Post-CYP17i Group	Number of participants with stable bone disease (no change). Radiographic bone progression was defined by the appearance of two or more new lesions on bone scan	3 months
Phase 1: Area Under the Plasma-Concentration-time Curve (AUCt) of ODM-201 at Steady-state	AUC(0-8h)	Day 8 predose 0 h and 0.5, 1, 1.5, 2, 4, 6 and 8 h postdose
Phase 1: Maximum Plasma Concentration (Cmax) of ODM-201 at Steady-state		Day 8 predose 0 h and 0.5, 1, 1.5, 2, 4, 6 and 8 h postdose
Phase 1: Time to Reach the Maximum Observed Concentration (Tmax) of ODM-201 at Day 1		1 day
Phase 1: Area Under the Plasma-Concentration-time Curve (AUCt) of Major Metabolite ORM-15341 at Steady-state	AUC(0-8h)	Day 8 predose 0 h and 0.5, 1, 1.5, 2, 4, 6 and 8 h postdose
Phase 1: Maximum Plasma Concentration (Cmax) of Major Metabolite ORM-15341 at Steady-state		Day 8 predose 0 h and 0.5, 1, 1.5, 2, 4, 6 and 8 h postdose
Phase 1: Time to Reach the Maximum Observed Concentration (Tmax) of Major Metabolite ORM-15341 at Day 1		1 day

Collaborators and Investigators

• Sponsor: Orion Corporation, Orion Pharma
• Collaborators: Endo Pharmaceuticals

Publications and helpful links

General Publications

• Fizazi K, Massard C, Bono P, Jones R, Kataja V, James N, Garcia JA, Protheroe A, Tammela TL, Elliott T, Mattila L, Aspegren J, Vuorela A, Langmuir P, Mustonen M; ARADES study group. Activity and safety of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomised phase 2 dose expansion trial. Lancet Oncol. 2014 Aug;15(9):975-85. doi: 10.1016/S1470-2045(14)70240-2. Epub 2014 Jun 25.

Helpful Links

• Lancet Oncology publication containing study results
• PubMed link to the Lancet Oncology publication containing study results

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: March 7, 2011
• First Submitted That Met QC Criteria: March 16, 2011
• First Posted (Estimate): March 17, 2011

Study Record Updates

• Last Update Posted (Actual): March 29, 2017
• Last Update Submitted That Met QC Criteria: February 9, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 3104001