metastatic Castration Resistant Prostate Cancer MedDRA version: 21.1 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: ModraDoc006
Pharmaceutical Form: Tablet
INN or Proposed INN: Docetaxel
CAS Number: 114977-28-5
Other descriptive name: ANHYDROUS DOCETAXEL
Concentration unit: mg milligram(s)
Concentrati
Sponsors
Modra Pharmaceuticals B.V.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Age = 18 years 2. Histologically or cytologically proven prostate cancer with evidence of progressive mCRPC, defined as: a. Castrate levels of testosterone, defined as = 50 ng/dL (or = 0.50 ng/mL or 1.73 nmol/L) b. Evidence of progressive metastatic disease as defined by radiographic disease progression or PSA progression c. With an indication for systemic treatment with docetaxel according to the standard of care 3. 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 4. Resolution of toxicity of prior therapy to 9.6 g/dL) b. ANC = 1.5 x 109 /L c. Platelet count = 100 x 109 /L d. Hepatic function defined by serum bilirubin = ULN, ALAT and ASAT = 1.5 x ULN concomitant with alkaline phosphatase = 2.5 × ULN. e. Renal function defined by serum creatinine = 1.5 x ULN or creatinine clearance = 50 ml/min (by Cockcroft-Gault formula, or MDRD). 6. WHO performance status of 0-2 7. Estimated life expectancy of at least 12 weeks 8. Able and willing to swallow oral medication 9. Able and willing to undergo radiologic scans (CT scan) 10. Able and willing to give written informed consent according to local guidelines Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: 1. 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. 2. Subjects who have had prior treatment with taxanes. 3. Subjects with symptomatic brain metastases. Subjects asymptomatic in the absence of corticosteroids and anticonvulsant therapy for =6 weeks are eligible. Radiotherapy for brain metastasis must have been completed =6 weeks prior to start of trial. Brain metastasis must be stable with verification by imaging (e.g. brain MRI or CT completed at screening, demonstrating no current evidence of progressive brain metastases). Subjects are not permitted to receive anti-epileptic drugs or corticosteroid treatment indicated for brain metastasis. Subjects with a history of leptomeningeal metastases are not eligible. 4. 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. 5. 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. 6. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) 7. Unresolved (>grade 0 as defined by CTCAE version 5.0) gastrointestinal toxicities (pre-existing mucositis, diarrhea or nausea/vomiting) 8. Grade = 2 motor or sensory neuropathy symptoms (as defined by CTCAE version 5.0) 9. Known hypersensitivity to any of the study drugs or excipients or taxanes 10. 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 11. Bowel obstruction or motility disorder that may influence the resorption of drugs as judged by the treating physician 12. Major surgical procedures within 21 days prior to providing informed consent 13. Active acute or chronic infection, which is not controlled by appropriate medication (at the discretion of the treating physician) 14. Known positivity for Human Immunodeficiency Virus HIV-1 or HIV-2 type 15. Patients with known active infection of hepatitis B, C, or E (patients who are anti-HBC positive but HBsAg negative are eligible to participate in this study) 16. 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 17. Evidence of any other medical conditions (such as treatment-resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, or pulmonary embolism within 4 weeks of randomization, or psychiatric illness, drug or alcohol abuse, physical examination or laboratory findings) that may interfere with the planned treatment, affect subject compliance or place the subject at high risk of treatment-related complications 18. Legal incapacity
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of ModraDoc006/r, as measured by RECIST version (v)1.1 criteria of objective response rate (ORR), compared to standard treatment with i.v. docetaxel in subjects with mCRPC.;Secondary Objective: • To evaluate the clinical outcome in terms of PSA response rate based on the Prostate Cancer Clinical Trials Working Group 3 (PCWG3), progression-free survival (PFS) at 6-months, time to progression (TTP), duration of response (DOR), disease control rate (DCR), PSA PFS and time to PSA progression of ModraDoc006/r compared to i.v. docetaxel.To assess the time to first skeletal event, defined as the time from randomisation to the occurrence of the first skeletal-related event (i.e. radiation therapy or surgery to bone, clinically apparent pathological bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain) compared to i.v. docetaxel. • To determine the safety and tolerability of ModraDoc006/r compared to i.v. docetaxel. • To compare subject’s Health Related Quality of Life (HRQoL) response of ModraDoc006/r to i.v. docetaxel;Primary end point(s): Objective Response Rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1;Timepoint(s) of evaluation of this end point: Tumour assessment (following PCWG3) by PSA prior to every cycle and imaging/radiological assessment (i.e. CT/MRI +/- bone scan) at baseline (= 7 days prior to start of intake of study medication) at the end of cycle 3 and cycle 6, every 4 cycles thereafter and at End of Treatment (EOT), according to the RECIST v1.1 criteria. Both PSA response and radiological response must be confirmed either after 4 weeks for PSA and after 4 weeks for RECIST v1.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints: o PSA response rate defined as PSA decline of >30% and >50% decline from baseline with confirmatory read =4 weeks later without clinical / imaging progressive disease (PD) based on the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) recommendations o Progression free survival (PFS) at 6 months based on RECIST v1.1 o PSA-PFS according to PCWG3 criteria o Time to PSA progression defined as the time from randomization to the time when the PSA increases by 50% above the nadir, as described in figure 5 o Time to first skeletal event, defined as the time from randomisation to the occurrence of the first skeletal-related event (i.e. radiation therapy or surgery to bone, clinically apparent pathological bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain) o Duration of response (DOR) based on RECIST v1.1 o Time to progression (TTP) based on RECIST v1.1, incorporating the bone metastatic variable according to PCWG3 o Disease control rate (DCR) Safety endpoints: o Incidence and severity of adverse events (AEs) according to NCI-CTCAE criteria (version 5.0) HRQoL endpoints: o Health Related Quality of Life (HRQoL) as assessed by FACT global, FACT-P and FACT-taxane, Treatment Satisfaction and EQ-5D questionnaires: o Overall HRQoL improvement o Improvements in the individual HRQoL domains o Time to HRQoL deterioration o Overall Health Related Utility;Timepoint(s) of evaluation of this end point: Tumour assessment => see item 5.1.1 Safety assessment: all visits FACT global, FACT-P and FACT-taxane, Treatment Satisfaction and EQ-5D questionnaire: Baseline, cycle 3 and 6 and after 10 cycles or end of treatment | — |
Countries
Czech Republic, Germany, Hungary, Poland, Russian Federation, United States
Contacts
Public ContactProject director
Modra Pharmaceuticals
Outcome results
None listed