A Multicentre Phase IIb Trial to Evaluate the Efficacy and Tolerability of ModraDoc006/r in Subjects with Metastatic Castration Resistant Prostate Cancer (mCRPC), Suitable for Treatment with a Taxane

This is a multicenter phase IIb study to evaluate the efficacy and tolerability of ModraDoc006 in combination with ritonavir (denoted ModraDoc006/r) in patients with metastatic castration-resistant prostate cancer, suitable for treatment with a taxane.

Inclusion Criteria:
• Histologically or cytologically proven prostate cancer with evidence of progressive mCRPC, defined as:
o Castrate levels of testosterone, defined as ≤ 50 ng/dL (or ≤ 0.50 ng/mL or 1.73 nmol/L)
o Evidence of progressive metastatic disease as defined by radiographic disease progression or PSA progression
o With an indication for systemic treatment with docetaxel according to the standard of care
• Measurable tumour lesions, defined as pelvic and/or extra-pelvic nodal lesions ≥1.5 cm in the short axis or visceral lesions ≥1.0 cm in the longest dimensions and measurable according to RECIST v1.1, bone metastasis as evaluated with 99mTc-methylene diphosphonate (MDP) radionuclide bone scintigraphy
• Resolution of toxicity of prior therapy to < grade 2 (except for alopecia), as defined by CTCAE v5.0
• Adequate haematological, renal and hepatic functions:
• Estimated life expectancy of at least 12 weeks
• Able and willing to swallow oral medication
• Able and willing to undergo radiologic scans (CT scan)
• Able and willing to give written informed consent according to local guidelines

Exclusion Criteria:
• Any treatment with investigational drugs, chemotherapy or immunotherapy within 4 weeks prior to receiving the first dose of investigational treatment. Palliative radiotherapy (1x8 Gy dose) is allowed before and during the study, but not in the week prior to start of study treatment.
• Subjects who have had prior treatment with taxanes.
• Subjects with symptomatic brain metastases.
• Current malignancies other than mCRPC with exception of adequately treated basal or squamous cell carcinoma of the skin, or adequately treated non-muscular invasive bladder cancer.
• Absence of highly effective method of contraception as of cycle one day one (C1D1). Men enrolled in this trial must agree to use a highly effective contraceptive method throughout the study.
• Uncontrolled hypertension
• Unresolved gastrointestinal toxicities
• Grade ≥ 2 motor ≥ 2 motor or sensory neuropathy symptoms
• Known hypersensitivity to any of the study drugs or excipients or taxanes
• Concomitant use of P-glycoprotein (P-gp , MDR), CYP3A, OATP1B1, OATP1B3 and MRP2 modulating drugs such as Ca+- entry blockers (verapamil, dihydropyridines), cyclosporine, quinidine and grapefruit juice, concomitant use of HIV medications, other protease inhibitors, (non) nucleoside analogues, or St. John's wort
• Bowel obstruction or motility disorder that may influence the resorption of drugs as judged by the treating physician
• Major surgical procedures within 21 days prior to providing informed consent
• Active acute or chronic infection, which is not controlled by appropriate medication (at the discretion of the treating physician)
• Clinically significant (i.e. active) cardiovascular disease defined as stroke, transient ischemic attack (TIA), myocardial infarction, unstable angina, or congestive heart failure within ≤ 6 months prior to first trial treatment
• Evidence of any other medical conditions that may interfere with the planned treatment, affect subject compliance or place the subject at high risk of treatment-related complications
• Legal incapacity
Phase IIb
Brendan Curti, M.D.
Modra Pharmaceuticals
  • Oncology and Hematology Care Westside
  • Providence Cancer Institute Clackamas Clinic
  • Providence Cancer Institute Franz Clinic
  • Providence Cancer Institute Newberg Clinic