None listed
Conditions
Brief summary
This is a first-in-human study of a new PLA2 inhibitor drug called c2. Who is it for? You may be eligible for this study if you are 18 or older and have prostate cancer confirmed by biopsy. Study details All participants in this study will receive the study drug (called c2), which is an oral pill. In the first part of the study, volunteers will be divided into 4 cohorts, each taking a different single dose of the medication. In the second part of the study, participants will take at a maximum of 10mg the study drug. Participants will be monitored for adverse events and medication efficacy, and provide blood and urine for analysis. It is hoped this research will provide evidence about this medication and lay the groundwork for future studies of this drug.
Interventions
There are 2 parts to this study
Part I: Single dose
All eligible patients will receive oral c2 tablet for single does (Part I).
c2 ( at the assigned dose) will be administered as a single oral dose at the start of a 14 day observation period for patient 1 in each cohort. Subsequent patients within the cohort will be enrolled after safety review of patient 1 by the DSMB.
At each dose level, beginning with Dose Level 1, three patients will be initially enrolled. If none of the first 3 pati
There are 2 parts to this study Part I: Single dose All eligible patients will receive oral c2 tablet for single does (Part I). c2 ( at the assigned dose) will be administered as a single oral dose at the start of a 14 day observation period for patient 1 in each cohort. Subsequent patients within the cohort will be enrolled after safety review of patient 1 by the DSMB. At each dose level, beginning with Dose Level 1, three patients will be initially enrolled. If none of the first 3 patients experiences a dose-limiting toxicity (DLT) then dose escalation will proceed to the next dose level. If one DLT is encountered in the first 3 patients in that dose level, then up to another 3 patients will be enrolled at that level. If another DLT occurs in that cohort, dose escalation will stop and Dose Level -1 (previous dose level) will be used for Part 2. Otherwise, dose escalation will proceed to the next dose level. The next dose level will be determined by agreement of the investigators and DSMB when all patients at the current dose level have completed 14 days of continuous dosing Dose Escalation Schedule Dose Level 1: 5 mg - 50% target dose Dose Level 2: 10 mg -100% target dose Dose Level 3: 40 mg - 400% target dose Dose Level 4: 100 mg - 1000% target dose Part II: oral c2 at a maximum of 10 mg daily, for a total of up to 6 weeks On completion of the observation period (14 days for each patient) for the cohort, the DSMB will conduct a safety review meeting to determine whether the cohort can Progress to Part 2. For repeat dosing (Part 2) participants will visit the hospital weekly for review of adverse events, physical examination and laboratory tests. A weekly supply of trial drug will dispensed by the Liverpool Cancer Therapy pharmacy at each visit. Participants will also be provided with a patient diary to record any possible adverse events ,
Sponsors
Prof Paul de Souza
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. At least 18 years of age. 2.Have provided written informed consent. 3.Evidence of prostate cancer: ( Biopsy evidence of adenocarcinoma of the prostate) 4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 5.Adequate organ function as follows: • Bone Marrow Reserve: absolute neutrophil count (ANC) equal to 1.5 x 109/L; platelet count equal to 100 x 109/L; haemoglobin equal to 9.0 g/dL. • Hepatic: bilirubin equal to 1.5 times the upper limit of normal (× ULN), alkaline phosphatase (AP), aspartate transaminase (AST), and alanine transaminase (ALT) equal to 3.0 × ULN (AP, AST, and ALT equal to 5 × ULN is acceptable if liver has tumor involvement). 6.Anticipated adequate venous access for pharmacokinetic sampling 7.Continuing androgen-ablative therapy without changes in prior 1 month 8.Documented metastatic disease 9.Male participants if sexually active agree to use highly effective methods of contraception for the period of the study, and for 90 days after the last day of treatment.
Exclusion criteria
1.Treatment within the last 30 days with a drug that has not received regulatory approval at the time of study entry. 2.Anti-tumour therapy (including chemotherapy, radiation therapy, targeted therapeutics or hormonal therapy) within the 30 days prior to first study therapy. Permitted exceptions are concurrent use of GnRH agonists or oral anti-androgens for prostate cancer at stable doses for at least 30 days prior to study entry. 3.Serious concomitant disorders (for example, heart failure) at the investigator’s discretion. 4.Presence of an uncontrolled, active infection requiring therapy (at the investigator’s discretion). 5.Central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy). 6.Inability to comply with protocol or study procedures. 7.ECOG performance status 2, 3 or 4.
Outcome results
None listed