Metastatic Castrate Sensitive Prostate Cancer (mCSPC) and metastatic Castrate Resistant Prostate Cancer (mCRPC) MedDRA version: 21.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10060862 Term: Prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA ver
Conditions
Interventions
Product Name: TAVT-45
Pharmaceutical Form: Granules for oral suspension in sachet
INN or Proposed INN: ABIRATERONE ACETATE
CAS Number: 154229-18-2
Current Sponsor code: TAVT-45
Other descriptive name:
Sponsors
Tavanta Therapeutics, Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Written informed consent obtained prior to any study-related procedure being performed 2. Male patients at least 18 years of age or older at time of consent 3. Pathologically confirmed adenocarcinoma of the prostate 4. Ongoing therapy with a gonadotropin releasing hormone (GnRH) agonist or antagonist (unless patient has already had a bilateral orchiectomy) AND serum testosterone level <50 ng/dL at screening 5. Have either metastatic CSPC or metastatic CRPC, as defined below: a). CSPC: Using the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) system, patients must have Tany Nany M+ (distant metastases) disease AND two of the following: -Gleason score of 8 or greater -Three or more bone scan lesions -Measurable visceral metastases b). CRPC: Patients must have metastatic* disease, and must also have disease progression according to the recommendations of the Prostate Cancer Working Group 3 by having at least one of the following criteria: -Two rises of PSA (taken a minimum of 1 week apart) from a baseline measurement of at least 1 ng/mL -Imaging progression (CT/MRI) by RECIST 1.1 criteria or PET/CT* -Nuclear scan progression by 2 or more new bone lesions. *Note: Metastatic disease should be documented by MRI/CT, PET/CT (including, but not limited to, standard of care imaging using 18F-fluciclovine, 11C-choline, or PSMA where approved) or bone scan. Imaging obtained within 90 days prior to the start of study drug/reference product will be accepted. 6. The following prior treatment and or surgery for prostate cancer are allowed: a) CSPC: i) Up to 90 days of androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists/antagonists or orchiectomy with or without concurrent anti-androgens prior to patients' randomization is permitted ii) Patients may have one course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease (e.g., impending cord compression or obstructive symptoms) if administered prior to randomization iii) Radiation or surgical therapy that was not initiated 4 weeks after the start of ADT or orchiectomy b) CRPC: i). Previous chemotherapy with docetaxel for metastatic disease with treatment completed at least 1 year prior to enrolment 7. Discontinuation of flutamide or nilutamide, and other anti-androgens prior to the start of study medication; discontinuation of bicalutamide prior to start of study medication 8. Discontinuation of strong CYP3A4 inducers at prior to start of study medication 9. Discontinuation of radiotherapy prior to start of study medication 10. Discontinuation of herbal supplements at least 4 weeks prior to the first dose of study medication and for the duration of the trial. 11. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at screening 12. Normal organ function with acceptable initial laboratory values within the screening period: ANC: = 1,500/µl Albumin: = 3.0g/dL Hemoglobin: = 9g/dL Platelet count: = 100,000/µl Serum Creatinine: = 3.0 x the institutional upper limit of normal (ULN) Potassium: = 3.5 mmol/L (within institutional normal range) Bilirubin: = 1.5 ULN (unless documented Gilbert's disease) SGOT (AST): = 2.5 x ULN SGPT (ALT): = 2.5 x ULN 13. Life expectancy of at least 6 months at screening 14. Patients engaged in sex with women of child-bearing potential agree to use a condom plus another effective contraception method. Patients agree to use a condom when engaged in any
Exclusion criteria
Exclusion criteria: 1. For mCSPC patients: any prior pharmacotherapy, radiation therapy, or surgery for metastatic prostate cancer not specified as allowable treatment in Inclusion Criterion 6. For example, prior therapy with apalutamide or enzalutamide is prohibited as well as therapy with an investigational agent as described in Exclusion Criterion 16. 2. For mCRPC patients: a) Prior treatment with abiraterone or enzalutamide is prohibited b) Previous chemotherapy is prohibited with exception of docetaxel treatment as specified in the inclusion criteria 6. 3. Initiation of bisphosphonate or denosumab therapy within 4 weeks prior to the start of study drug/reference product. Patients who are on a stable dose of these medications for at least 4 weeks at the time of starting study drug/reference product will be eligible. 4. Therapy with estrogen within 4 weeks prior to the start of study drug 5. Use of systemic glucocorticoids equivalent to >10 mg prednisone daily. Patients who have discontinued or reduced dosing to the equivalent of = 10 mg prednisone daily within 14 days prior to the start of study drug are eligible 6. Known, symptomatic metastases to the brain or central nervous system involvement (patients with asymptomatic and neurologically stable disease for the past 4 weeks will be permitted) 7. History of adrenal gland dysfunction defined as requiring treatment for adrenal insufficiency 8. History of other malignancy within the previous 2 years (no longer being actively treated), with the exceptions of basal cell carcinoma, non-muscle invasive bladder cancer that has been treated and is under surveillance, or other in-situ cancers with a low likelihood of recurrence 9. Major surgery within 4 weeks prior to the start of study drug 10. Known gastrointestinal disease or condition that could impair absorption inclusive of gastrocolic fistula, gastroenterostomy, biliary obstruction, cirrhosis, chronic pancreatitis or pancreatic cancer, cystic fibrosis, lactate deficiency, amyloidosis, celiac disease, Crohn’s disease, radiation enteritis, intestinal resection, and history of bariatric surgery 11. Known history of human immunodeficiency virus or seropositive test for hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg) (note: HCV patients with undetectable viral load will be eligible) 12. Poorly controlled diabetes, defined as HbA1c > 8% within the past 12 months 13. Uncontrolled hypertension at screening 14. History of New York Heart Association class III or IV heart failure 15. Serious concurrent illness, including psychiatric illness, that could interfere with study participation 16. Receipt of another investigational agent within 4 weeks or 5 x the treatment half-life, whichever is longer, of treatment start. 17. Known hypersensitivity or allergy to abiraterone acetate, prednisone or any excipients in the study drugs 18. In the opinion of the investigator, participation in the trial would prevent the patient from receiving local standard-of-care treatment for metastatic prostate cancer, if clinically indicated, after completion of the trial . 19. Other condition which, in the opinion of the Investigator, would preclude participation in this trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Establish equivalence between TAVT-45 granules and Zytiga tablets in patients with metastatic Castrate Sensitive Prostate Cancer (mCSPC) and metastatic Castrate Resistant Prostate Cancer (mCRPC).;Secondary Objective: Characterize the multiple-dose pharmacokinetic profile of TAVT-45 in a cohort of patients.;Primary end point(s): Efficacy: The primary efficacy endpoint is the comparison of the average of serum testosterone levels on days 9 and 10 between groups (TAVT-45 vs R-AA). Safety: Safety endpoints include incidence of treatment emergent adverse events (TEAE), and clinically relevant changes in vital signs and laboratory assessments. Pharmacokinetics: For a cohort of up to 8 patients randomized to TAVT-45 and participating in the serial PK sampling on Day 1 and Day 9, the following PK parameters will be determined: a) Area under the concentration-time curve from time zero to 12 hours post dose (AUC0-12) b) Maximum measured plasma concentration (Cmax) c) Minimum measured plasma concentration (Cmin) d) Time to maximum measured concentration (tmax) e) Accumulation ratio (Rac) f) Effective half-life (t½);Timepoint(s) of evaluation of this end point: Average of serum testosterone levels will be compared between groups on Days 9 and 10. A cohort of 8 patients randomized to TAVT-45 will participate in serial PK sampling on Days 1 and 9. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary efficacy endpoint is the PSA-50 response, defined as a decrease of =50% in PSA levels from baseline at any time over the 84-day post-treatment period. Other secondary efficacy endpoints are as follows: a) Serum testosterone levels at Days 28, 56 and 84 b) PSA-50 response at Days 28, 56 and 84 c) PSA levels at Days 28, 56 and 84 d) Trough concentrations of abiraterone at Days 9, 28, 56 and 84 ;Timepoint(s) of evaluation of this end point: a) Serum testosterone levels at Days 28, 56 and 84 b) PSA-50 response at Days 28, 56 and 84 c) PSA levels at Days 28, 56 and 84 d) Trough concentrations of abiraterone at Days 9, 28, 56 and 84 | — |
Countries
France, Germany, Hungary, Poland, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactRegulatory Affairs
Tavanta Therapeutics, Inc.
Outcome results
None listed