Open-label Dose Escalation Phase 1b Trial of a New Micellar Docetaxel Compound in Patients With mCRPC

Inclusion Criteria:

* Written informed consent according to Swiss law and ICH GCP E6(R2) regulations before registration and prior to any trial specific procedures.
* Histologically confirmed adenocarcinoma of the prostate
* Metastatic castration resistant, progressive disease as defined as per PCWG3 criteria
* Ongoing concurrent use of GnRH agonist or antagonist is required if the patient has not been surgically castrated
* Measurable or evaluable disease per Recist 1.1 and as per PCWG3
* Patients with treated and stable CNS metastases are eligible, provided they meet the following criteria:

  * No ongoing requirement for corticosteroids as therapy for symptomatic CNS disease; anticonvulsants at a stable dose allowed
  * No stereotactic radiation or whole-brain radiation within 7 days prior to registration,
  * No evidence of progression for at least 4 weeks after completion of CNS-directed therapy as verified by clinical examination and brain imaging (MRI or CT) during the screening period
* Patients with a previously treated malignancy are eligible, when the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low.
* Age ≥ 18 years
* ECOG performance status 0-1
* Adequate bone marrow function: (patient must not have received any growth factor or blood transfusion within 7 days prior to registration): neutrophil count ≥ 1.5 x 109/L , platelet count ≥ 100 x 109/L, hemoglobin ≥ 80 g/L
* Adequate hepatic function: total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's disease 3.0 x ULN), AST and ALT ≤ 2.5 x ULN
* Adequate renal function: estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 (according to CKD-EPI formula)
* Willingness to have a central venous line inserted (PICC or Porth-a-Cath) if not already present.
* Men agree not to donate sperm or to father a child during trial treatment and until 6 months after the last dose of investigational drug. Sexually active patients must agree to have an effective contraception during study treatment and for 6 months after the last dose.

Exclusion Criteria:

* Clinical or radiological evidence of spinal cord compression
* Known predominant small cell or neuroendocrine component on histological diagnosis
* Prior chemotherapy including docetaxel for the treatment of prostate cancer (previous administration of chemotherapy concomitant with ADT is not allowed )
* Prior use of taxane-based chemotherapy for any other previous cancer
* Prior systemic treatment, immunotherapy, hormonal therapy (with the exception of GnRH agonists or antagonists) or investigational agents within 21 days before registration, with the exception of palliative radiotherapy (within 2 weeks)
* Concomitant or within 28 days of registration treatment with any other experimental drug (enrollment in another clinical trial except participation in SAKK 96/12 and/or 63/12\]
* Concomitant use of other anti-cancer drugs (other than GnRH agonists or antagonists). Bone-modifying agents (such as bisphosphonates or denosumab) are allowed before study entry and during treatment.
* Patients who have not recovered to CTCAE grade ≤1 from clinically relevant adverse events of prior therapies, except for residual toxicities, such as alopecia, which do not pose an ongoing medical risk.
* Peripheral neuropathy \> CTCAE grade 1
* Localized or general edema \> CTCAE grade 1
* Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV; unstable angina pectoris, history of myocardial infarction within the last six months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia), known significant QT-prolongation, uncontrolled hypertension.
* Major surgery within 4 weeks prior to registration
* Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment.
* Concomitant or prior use of immunosuppressive medication within 28 days before registration, with the exceptions of intranasal and inhaled corticosteroids, or systemic corticosteroids which must not exceed 10 mg/day of prednisone or a dose equivalent corticosteroid)
* Concomitant treatment with strong CYP3A inducers or inhibitors
* Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information
* Known hypersensitivity to trial drug(s) or to any component of the trial drug(s)
* 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.