Content - SAKK 08/16

SAKK 08/16 - Maintenance therapy for advanced prostate cancer

In this trial we will examine how well the medicinal product ODM-201 works as maintenance therapy for advanced prostate cancer following chemotherapy. The term maintenance therapy is used to describe preventive further treatment after successful completion of a preceding treatment (in the case of prostate cancer this is chemotherapy). With advanced prostate cancer, there is usually a break in treatment following chemotherapy with regular checks. In this trial we will examine whether early use of the medicine ODM-201 can improve the symptoms. It may thus be possible to delay recurrence of this cancer.  

ODM-201 belongs to a group of new active substances that are very effective in inhibiting the impact of testosterone on the cancer cells. It blocks the binding site for the growth hormone testosterone and thus obstructs signal transmission in the cancer cell. This causes the tumor to stop growing. This medicinal product has not yet been approved either in Switzerland or any other country. However, the active substance has undergone several clinical trials in humans in which the optimum dose was determined and general good tolerability was demonstrated.

Study Chair:

Prof. Dr. med. Silke Gillessen, Cantonal Hospital of St.Gallen, +41 71 494 10 92

  • Contacts at the hospitals

  • 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 OR enzalutamide for at least 8 weeks prior to taxane based chemotherapy

    • No evidence of disease progression after chemotherapy with docetaxel (cumulative dose of ≥ 450 mg/m2 or total dose ≥900mg) or cabazitaxel (cumulative dose of ≥120 mg/m2 or total dose ≥204 mg)

      • No evidence of progression on imaging according to PCWG3 [46]
      • 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
    • Retreatment with a taxane for metastatic castration resistant prostate cancer after interruption of > 8 weeks
    • 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.

Locations for this trial:

Kantonsspital Baden
Im Ergel 1
4600 Baden
Istituto Oncologico della Svizzera Italiana IOSI
Via Ospedale
0 6500 Bellinzona
Kantonsspital Graubünden
Loëstrasse 170
7000 Chur
Hôpital Fribourgeois HFR
Chemin des Pensionnats 2
1708 1708 Fribourg
Fondazione Oncologia Lago Maggiore
Via Antonio Ciseri 19
0 6600 Locarno
Kantonsspital Liestal
Rheinstrasse 26
0 4410 Liestal
Spital STS AG Thun
Krankenhausstrasse 12
0 3600 Thun
Kantonsspital St. Gallen
Rorschacher Strasse 95
0 9007 St. Gallen
Spital Thurgau, Kantonsspital Münsterlingen
Spitalcampus 1
0 8596 Münsterlingen
Hôpital du Valais Sion
Avenue du Grand-Champsec 80
0 1951 Sion