ODM-201 Maintenance Therapy in Patients With mCRPC Previously Treated With Novel Hormonal Agents.

Sponsor

Swiss Group for Clinical Cancer Research (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02933801

Collaborator

(none)

Enrollment

Locations

Arms

116

Anticipated Duration (Months)

2.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main objective of the trial is to assess impact of maintenance therapy with ODM-201 on radiographic progression-free survival (rPFS) of patients with mCRPC pretreated with novel hormonal agents who have non-progressive disease after chemotherapy with a taxane.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer Metastatic Prostate Cancer	Drug: ODM-201 Other: Placebo	Phase 2

Detailed Description

The treatment of metastatic castration-resistant prostate cancer has evolved rapidly over the past few years. First line treatment with one of the novel antihormonal drugs abiraterone or enzalutamide followed by chemotherapy with docetaxel is now standard of care. If a patient has disease stabilization on chemotherapy he undergoes a watchful waiting period and further treatment is only started at the time of disease progression. This trial tests the immediate use of the novel androgen receptor antagonist ODM-201 as maintenance treatment after chemotherapy aiming at prolonging radiographic progression free survival as compared to watchful waiting.

Study Design

Study Type:

Interventional

Actual Enrollment :

92 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

ODM-201 Maintenance Therapy in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC) Previously Treated With Novel Hormonal Agents and Non-progressive Disease After Subsequent Treatment With a Taxane: A Multicenter Randomized Double-blind Placebo-controlled Phase II Trial.

Actual Study Start Date :

Mar 31, 2017

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: ODM-201 600mg ODM-201 BID (twice daily) and Best Supportive Care until progression	Drug: ODM-201 ODM-201 will be given at a dose of 600 mg BID orally on a continuous basis. Other Names: BAY-1841788
Placebo Comparator: Arm B: Placebo Placebo BID (twice daily) and Best Supportive Care until progression	Other: Placebo Placebo will be given at a dose of 600 mg BID orally on a continuous basis.

Arm

Intervention/Treatment

Experimental: Arm A: ODM-201

600mg ODM-201 BID (twice daily) and Best Supportive Care until progression

Drug: ODM-201

ODM-201 will be given at a dose of 600 mg BID orally on a continuous basis.

Other Names:

BAY-1841788

Placebo Comparator: Arm B: Placebo

Placebo BID (twice daily) and Best Supportive Care until progression

Other: Placebo

Placebo will be given at a dose of 600 mg BID orally on a continuous basis.

Outcome Measures

Primary Outcome Measures

Radiographic progression-free survival (rPFS) at 12 weeks [At 12 weeks after treatment start]
Radiographic progression-free survival is defined as the time from treatment start to radiographic disease progression or death from any cause, whichever occurs earlier.

Secondary Outcome Measures

Radiographic progression-free survival (rPFS) [Every 12 weeks until disease progression (estimated up to 1 year)]
Radiographic progression-free survival is defined as the time from treatment start to radiographic disease progression or death from any cause, whichever occurs earlier.
Time to PSA progression [PSA level at baseline and every 4 weeks until disease progression (estimated up to 1 year)]
PSA progression is defined as: In case PSA levels had not decreased under treatment with the study drug: ≥ 25% increase over baseline (last PSA measurement before treatment start) AND an increase in the absolute PSA value of ≥ 5 ng/mL. In case of PSA response < 50% under treatment with the study drug: ≥ 25% increase over the nadir AND an increase in the absolute PSA value of ≥ 5 ng/mL. In case of PSA response ≥ 50% under treatment with the study drug: ≥ 50% increase over the nadir AND an increase in the absolute PSA value of ≥ 5 ng/mL
Time to symptomatic/clinical progression [treatment start to the time point of symptomatic/clinical progression (estimated up to 1 year)]
Symptomatic/clinical progression is defined by one of the following: Occurrence of a SRE due to bone metastases, defined as pathologic fracture, spinal cord compression, palliative radiation to bone, or surgery to bone Treating physician decides for intervention due to new disease related complications (e.g., urinary obstruction, hydronephrosis)
Event-free survival [treatment start until the event of interest (estimated up to 1 year)]
Event-free survival is defined as the time from treatment start until the event of interest.
Overall survival [time from trial randomization to the date of death from any cause (estimated up to 6 years)]
Overall survival is defined as the time from treatment start until death from any cause.
PSA response (30%, 50%, 90% and best) [PSA level at baseline and every 4 weeks until disease progression (estimated up to 1 year)]
30% PSA response is defined as a decrease in PSA level of at least 30% (compared to baseline PSA). 50% PSA response is defined as a decrease in PSA level of at least 50% (compared to baseline PSA). 90% PSA response is defined as a decrease in PSA level of at least 90% (compared to baseline PSA). Best PSA response is defined as the percentage of change in PSA from baseline to the maximum decline in PSA at any point under treatment. If there is a steady increase after baseline, the best response is defined as the percentage of change in PSA from baseline to the minimum increase in PSA at any point under treatment. Baseline is defined as the latest recorded measurement prior to the first dose of trial treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Written informed consent according to Swiss law and ICH/GCP regulations before registration and prior to any trial specific procedures not part of normal medical care.
Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate
Castration resistance: tumor progression after orchiectomy or during treatment with GnRH analogues (agonists or antagonists)
Metastatic disease, documented by imaging
Total testosterone ≤ 50 ng/dL (≤ 1.7 nmol/L)
Treatment with abiraterone AND/OR enzalutamide for at least 8 weeks prior to taxane based chemotherapy
No evidence of disease progression after chemotherapy with docetaxel (at least cumulative dose of ≥ 300 mg/m2 or total dose ≥ 600mg) or cabazitaxel (at least cumulative dose of ≥ 80 mg/m2 or total dose ≥ 160 mg)
No evidence of progression on imaging according to PCWG3
No evidence of progression on PSA levels referred to the nadir since start of taxane treatment (PSA progression defined as > 25% increase of PSA level or >50% if PSA decrease under chemotherapy >50% AND > 5 ng/mL increase in the absolute PSA value)
Non-surgically castrated patient agrees on ongoing use of GnRH analogues (agonists or antagonists) during the trial
Planned start of trial treatment 2 to 8 weeks after last taxane dose
Male patient 18 years or older
WHO performance status of ≤2
Laboratory values as specified below
alanine aminotransferase (ALT) ≤ 2.5 x ULN (except for patients with liver metastases ≤ 5.0 x ULN)
Total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's disease ≤ 3.0 x ULN)
Estimated creatinine clearance using the Cockcroft-Gault formula > 30 mL/minute
Blood counts at screening: haemoglobin ≥ 90 g/L, absolute neutrophil count ≥ 1500/μl (1.5x109/L), platelet count ≥ 100,000/μl (100x109/L) (patient must not have received any growth factor or blood transfusion within 7 days of the haematology laboratory obtained at screening)
Adequate cardiac function: Left ventricular Ejection Fraction (LVEF) ≥ 40% as determined by echocardiography (ECHO)
Patient is able and willing to swallow trial drug as whole tablet
Sexually active male subjects must agree to use condoms as an effective barrier method and refrain from sperm donation, and/or their female partners of reproductive potential to use a method of effective birth control, during the study treatment and for 3 months after the end of the treatment.
Patient agrees to participate in the mandatory translational research project

Exclusion Criteria:

Prior chemotherapy for prostate cancer except from chemotherapy with a taxane
Concurrent disease requiring higher doses of corticosteroid than the equivalent of 10 mg prednisone per day
Known CNS or leptomeningeal metastases
Clinical or radiological evidence of current spinal cord compression
History of hematologic or primary solid tumor malignancy, unless in remission for at least 2 years from registration with the exception of localized non-melanoma skin cancer or carcinoma in situ having undergone complete resection.
Prior therapy for mCRPC with modern anti-hormonal treatment except for enzalutamide or abiraterone
Concurrent treatment with other experimental drugs or treatment in a clinical trial within 30 days prior to trial entry (except clinical trial SAKK 96/12)
Concomitant use of other anti-cancer drugs or radiotherapy except for local pain control and GnRH analogues
Severe or uncontrolled cardiovascular disease
Acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before expected start of treatment
ECG abnormalities of Q-wave infarction, unless identified ≥ 6 months prior to registration or QTc interval >480 msec
Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of ODM-201
Known hypersensitivity to trial drug or to any component of the trial drug
Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Institut Bergonié	Bordeaux	France	33076
2	Centre Oscar Lambret	Lille	France	59020
3	Centre de lutte contre le cancer Léon Bérard	Lyon	France	69008
4	Centre Eugène Marquis	Rennes	France	35042
5	European Institute of Oncology (EIO)	Milano	Italy	20141
6	Istituto Nazionale dei Tumori - IRCCS Fondazione	Milano	Italy	20141
7	Istituto Nazionale dei Tumori - IRCCS Fondazione Pascale S.C.	Napoli	Italy	80131
8	AOU "Maggiore della Carità" di S.C. di Oncologia	Novara	Italy	28100
9	AOU San Luigi Gonzaga	Orbassano	Italy	10043
10	AO San Camillo and Forlanini Hospitals	Roma	Italy	00152
11	Presidio Ospedaliero Santa Chiara	Trento	Italy	38122
12	Azienda Ospedaliera Universitaria Integrate Verona (AOUI)	Verona	Italy	37126
13	Hospital de Torrecárdenas	Almería	Spain	04009
14	Hospital Universitario Infanta Cristina	Badajoz	Spain	06080
15	Hospital Clinic Barcelona	Barcelona	Spain	08036
16	Consorcio Hospitalario Provincial de Castellon	Castellón De La Plana	Spain	12002
17	Hospital Universitario San Cecilio	Granada	Spain	18016
18	Hospital Univ. de Guadalajara	Guadalajara	Spain	19002
19	Centro Integral Oncológico Clara Campal - Hospital Universitario HM Sanchinarro	Madrid	Spain	28050
20	Hospital Universitario Puerta de Hierro-Majadahonda	Majadahonda	Spain	28222
21	Hospital General Universitario Morales Meseguer	Murcia	Spain	30008
22	Complejo Hospital Universitario de Santiago de Compostela	Santiago De Compostela	Spain	15706
23	Kantonsspital Baden	Baden	Switzerland	CH-5404
24	Istituto Oncologico della Svizzera Italiana (IOSI)	Bellinzona	Switzerland	6500
25	Kantonsspital Graubuenden	Chur	Switzerland	7000
26	Hôpital Fribourg HFR	Fribourg	Switzerland	1708
27	Kantonsspital Liestal	Liestal	Switzerland	CH-4410
28	Fondazione Oncologia / Oncologia ematologia	Locarno	Switzerland	6600
29	Kantonsspital Muensterlingen	Münsterlingen	Switzerland	8596
30	Hôpital du Valais (Sion et Martigny)	Sion	Switzerland	1951
31	Kantonsspital - St. Gallen	St. Gallen	Switzerland	CH-9007
32	Spital STS AG	Thun	Switzerland	CH-3600