Clinical trial NCT02933801: ODM-201 Maintenance Therapy in Patients With mCRPC Previously Treated With Novel Hormonal Agents.
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Prostate Cancer Metastatic
Prostate Cancer
Keywords: metastatic castration resistant prostate cancer (mCRPC)
Prostate Cancer
phase II trial
ODM-201
maintenance therapy
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2016-10-14
Enrollment: 92
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Radiographic progression-free survival (rPFS) at 12 weeks
timeFrame: At 12 weeks after treatment start
Secondary outcomes:
measure: Radiographic progression-free survival (rPFS)
timeFrame: Every 12 weeks until disease progression (estimated up to 1 year)
measure: Time to PSA progression
timeFrame: PSA level at baseline and every 4 weeks until disease progression (estimated up to 1 year)
measure: Time to symptomatic/clinical progression
timeFrame: treatment start to the time point of symptomatic/clinical progression (estimated up to 1 year)
measure: Event-free survival
timeFrame: treatment start until the event of interest (estimated up to 1 year)
measure: Overall survival
timeFrame: time from trial randomization to the date of death from any cause (estimated up to 6 years)
measure: PSA response (30%, 50%, 90% and best)
timeFrame: PSA level at baseline and every 4 weeks until disease progression (estimated up to 1 year)
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonié
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre de lutte contre le cancer Léon Bérard
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Milano
country: Italy
facility: European Institute of Oncology (EIO)
city: Milano
country: Italy
facility: Istituto Nazionale dei Tumori - IRCCS Fondazione
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori - IRCCS Fondazione Pascale S.C.
city: Novara
country: Italy
facility: AOU "Maggiore della Carità" di S.C. di Oncologia
city: Orbassano
country: Italy
facility: AOU San Luigi Gonzaga
city: Roma
country: Italy
facility: AO San Camillo and Forlanini Hospitals
city: Trento
country: Italy
facility: Presidio Ospedaliero Santa Chiara
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrate Verona (AOUI)
city: Almería
country: Spain
facility: Hospital de Torrecárdenas
city: Badajoz
country: Spain
facility: Hospital Universitario Infanta Cristina
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Castellón De La Plana
country: Spain
facility: Consorcio Hospitalario Provincial de Castellon
city: Granada
country: Spain
facility: Hospital Universitario San Cecilio
city: Guadalajara
country: Spain
facility: Hospital Univ. de Guadalajara
city: Madrid
country: Spain
facility: Centro Integral Oncológico Clara Campal - Hospital Universitario HM Sanchinarro
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro-Majadahonda
city: Murcia
country: Spain
facility: Hospital General Universitario Morales Meseguer
city: Santiago De Compostela
country: Spain
facility: Complejo Hospital Universitario de Santiago de Compostela
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana (IOSI)
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Fribourg
country: Switzerland
facility: Hôpital Fribourg HFR
city: Liestal
country: Switzerland
facility: Kantonsspital Liestal
city: Locarno
country: Switzerland
facility: Fondazione Oncologia / Oncologia ematologia
city: Münsterlingen
country: Switzerland
facility: Kantonsspital Muensterlingen
city: Sion
country: Switzerland
facility: Hôpital du Valais (Sion et Martigny)
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
city: Thun
country: Switzerland
facility: Spital STS AG
Study officials:
affiliation: Cantonal Hospital of St. Gallen
name: Silke Gillessen, Prof
role: STUDY_CHAIR
References: