• Advanced prostate cancer • Advanced epithelial ovarian cancer, advanced squamous cell carcinoma of the cervix, advanced breast cancer, endometrial cancer, and salivary gland cancer that are poorly responsive to standard treatment options MedDRA version: 16.0 Level: PT Classification code 10061934 Term: Salivary gland cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 16.0 Level: PT Classification code 10060862 Term:
Conditions
Interventions
Product Code: OPB-111001 5mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: NA
Current Sponsor code: OPB-111001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentrati
Sponsors
Otsuka Novel Products GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The patient should meet the following inclusion criteria to be considered for enrollment into the study 1. Patients =18 years of age at Screening 2. Patients with prostate cancer that is recurrent or did not respond to previous hormone therapy and/or who have exhausted standard treatment options. For the dose escalation parts only: Patients with any of the following diseases who have exhausted standard treatment options: a. recurrent or refractory ovarian cancer b. recurrent or refractory cervical squamous cell carcinoma c. recurrent or refractory breast cancer d. recurrent or refractory salivary gland cancer e. recurrent or refractory endometrial cancer 3. Histologically or cytologically documented diagnosis of cancer 4. Measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST), Version 1.1 or a. for prostate cancer also evaluable disease (nonmeasurable) defined as prostate-specific antigen progression according to Prostate Cancer Working Group 2 eligibility criteria b. for ovarian cancer also evaluable disease (nonmeasurable) according to the Gynaecologic Cancer Intergroup 5. Absolute neutrophil count =1.5 (1500/mm3) and platelets =100 × 10E9/L (without platelet transfusion within the last 4 weeks before first study drug administration), and haemoglobin =9 g/dL at Screening 6. Alanine aminotransferase and aspartate aminotransferase =2.5 × the upper limit of normal (ULN), Total bilirubin =1.5 × ULN (exception: patients with liver metastasis are allowed to have aspartate aminotransferase =5 × ULN and alanine aminotransferase =5 × ULN) at screening 7. Albumin =26 g/L at Screening 8. Estimated life expectancy >3 months (as judged by investigator) 9. Eastern Cooperative Oncology Group performance status =1 10. In prostate cancer patients: ongoing therapy with luteinizing hormone releasing hormone analogue or orchiectomy 11. Agreement of female patients of childbearing potential and male patients who have partners capable of reproduction to use an effective double-barrier contraceptive method during the course of the study and for 3 months following the completion of their last treatment. Females of childbearing potential must have a negative beta-human chorionic gonadotropin pregnancy test result within 3 days of the first study drug administration. Female patients who are surgically sterilized or who are >45 years old and have not experienced menses for >2 years may have the beta-human chorionic gonadotropin pregnancy test waived. 12. Ability to understand and give written informed consent and to comply with the protocol (i.e., with all study-related procedures, medication use, and evaluations) Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Concurrent prior treatment-related toxicity of Grade 2 or higher. Exception: any toxicity that is in the view of the investigator not a clinically significant safety risk for IMP administration. 2. Previous treatment with cytotoxic chemotherapy or other anticancer therapy within 4 weeks before the first dosing with study drug (at least 6 weeks for mitoxantrone, nitrosurea, and bicalutamide). 3. Treatment with systemic glucocorticosteroids of more than a 2 mg dexamethasone equivalent (e.g., 13 mg prednisolone) per day or in cases of treatment with =2 mg dexamethasone equivalent per day: a. Dosing was changed within 6 weeks before Screening or b. The patient’s cancer is responding to glucocorticosteroid intake(as by investigator judgment) 4. Radiation therapy within 4 weeks prior to the first dosing with IMP. 5. Treatment with a systemic IMP in a clinical trial within 28 days before the Screening visit. 6. Use of prohibited medications within 21 days of the first dose of IMP. 7. Current or past history of clinically significant gastrointestinal disease or major gastrointestinal surgery, malabsorption syndrome, or other conditions that could interfere with enteral absorption. 8. Significant uncontrolled cardiovascular disease or cardiac insufficiency (New York Heart Association classes III to IV) or a history of ventricular arrhythmia requiring medication. 9. Patients with symptomatic central nervous system metastasis. 10. History of positive human immunodeficiency virus test result (enzyme-linked immunosorbent assay or Western blot) 11. Clinical or laboratory evidence of active or chronic hepatitis B or hepatitis C infection. 12. Major surgery =4 weeks before the first study drug administration or ongoing side effects of previous major surgery. 13. Concurrent clinically significant unrelated systemic illness (e.g., serious infection) or significant pulmonary, hepatic, or other organ dysfunction that would compromise the patient’s ability to tolerate study treatment or would likely interfere with study procedures or results. 14. Active treatment/chemotherapy for another primary malignancy within the past 3 years (except for nonmelanoma skin cancer and cervical carcinoma in situ). 15. Women who are pregnant or breastfeeding. 16. Known or suspected hypersensitivity to the excipients (ingredients) in the study drug formulation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The principal objective of this clinical study is to find out how well the patients can tolerate OPB-111001 and to find the maximum tolerated dose in patients with cancer of the prostate, ovary, cervix, endometrium, breast, or salivary gland;Secondary Objective: The secondary objective is to look at how the drug responds in the body when administrated to a patient and its initial effect on the type of cancer. ;Primary end point(s): The primary outcome measures are the determine the safety and tolerability of OPB111001 in order to establish an MTD and recommended phase II dose. This will be achieved by monitoring the incidence of AEs (defined by NCI CTCAE V4), along with vital signs, clinical laboratory parameters and electrocardiography assessments.;Timepoint(s) of evaluation of this end point: 1) MTD/RP2D - Dose Escalation Part: After 1 or 3 cycles of treatment, Tolerability: Continuously | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Pharmacokinetic parameters for OPB-111001 and its metabolites: Area under the curve (AUC), maximum plasma drug concentration after single dose administration (Cmax), time to maximum plasma drug concentration after single dose administration (tmax)and terminal elimination half-life, t1/2 and for OPB- 111001: Systemic clearance(CL/F) 2) Assessment of antitumour activity as defined by Response Evaluation Criteria in Solid Tumours (RECIST), Version 1.1: complete response(CR), partial response (PR), stable disease (SD), objective response rate(ORR) (CR + PR) 3) Prostate-specific antigen (PSA) response in patients with prostate cancer: relative change determined according to Prostate Cancer Working Group 2 (PCWG2) 4) CA125 response in patients with ovarian cancer: relative change determined according to the Gynaecologic Cancer Intergroup (GCIG) 5) Time to Treatment Failure (TTF);Timepoint(s) of evaluation of this end point: 1), 2), 3), 4) Repeatedly until end of study; 5) At end of study | — |
Countries
United Kingdom
Contacts
Public ContactClinical Program Leader
Otsuka Novel Products GmbH
Outcome results
None listed