Cancer
Conditions
Interventions
Not Applicable. No Control group
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1 Capable of giving signed informed consent. 2 Provision of signed and dated written ICF prior to any mandatory study-specific procedures, sampling, and analyses. 3 Must be 18 years of age or older at the time of signing the ICF. 4 ECOG Performance Status of 0 or 1. 5 Anticipated life expectancy = 3 months in the opinion of the Investigator. 6 Histologically confirmed diagnosis of adenocarcinoma of the prostate or neuroendocrine differentiated prostate cancer. 7 Must have had prior bilateral orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L). 8 At least one metastatic lesion present on baseline CT, MRI, or bone scan obtained = 28 days prior to the first dose of IMP. Participants may have non-measurable (per RECIST 1.1) lesions including bone only metastases. Adequate organ function as indicated by the following laboratory values: (a) Hematologic*: (i) ANC = 1500/mm3(= 1.5 × 109/L) (ii) Platelet count = 100,000/mm3(= 100 × 109/L) (iii) Hemoglobin = 9.0 g/dL (= 90 g/L) *Hematologic criteria cannot be met with ongoing or recent blood transfusions (within 7 days prior to the scheduled first dose of IMP) or require growth factor support (within 21 days prior to the scheduled first dose of IMP). (b) Cardiac: (i) Resting QTcF = 450 msec (c) Renal: (i) Creatinine clearance = 60 mL/min (calculated by Cockcroft-Gault formula) (d) Hepatic: (i) AST and ALT = 3.0 × ULN (= 5 × ULN in participants with known liver metastasis) (ii) Serum total bilirubin = 1.5 × ULN (= 3 x ULN in participants with Gilbert’s disease) 10 In the judgment of the Investigator, the participant is expected to be compliant and have a high probability of completing the study. 11 Agree to avoid unprotected sex for the duration of study participation and agree to follow the lifestyle and contraception guidelines.
Exclusion criteria
Exclusion criteria: 1 Treatment with any radiopharmaceutical within 6 weeks of the first dose of an IMP. 2 RT or EBRT within 28 days prior to the first dose of IMP and all RT-related events have not recovered to Grade = 1. 3 Administration of any systemic cytotoxic or investigational therapy = 28 days of the first dose of IMP or 5 half-lives, whichever is shorter. (a) Part A Only: Participants receiving ARPI (eg, abiraterone, enzalutamide) may continue this therapy during imaging procedures, but must undergo appropriate washout as described above prior to receiving first dose of AZD2284, if eligible. 4 All prior treatment-related adverse events must have resolved to Grade = 1 (CTCAE v5.0). Alopecia and stable persistent Grade 2 peripheral neuropathy may be allowed at the discretion of the Investigator. 5 A history of CNS metastases, except those who have received therapy (surgery, radiotherapy, gamma knife) and are neurologically stable, asymptomatic, and not receiving corticosteroids to maintain neurologic integrity for a minimum of 28 days. Participants with epidural disease, canal disease, and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For participants with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast) 6 Symptomatic cord compression or clinical or radiologic findings indicative of impending cord compression. 7 Contraindications to or inability to perform the imaging procedures required in this study (eg, inability to lay flat for the image acquisitions, etc). 8 Previous or concurrent cancer that is distinct from the cancer under investigation in primary site or histology, except treated cutaneous basal cell carcinoma or squamous cell carcinoma, and superficial bladder tumors. Any cancer curatively treated > 2 years prior to the first dose of IMP is permitted.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| -Evaluate the safety and tolerability of AZD2284, AZD2287, and AZD2275. Determine the RP2D of AZD2284. | — |
Secondary
| Measure | Time frame |
|---|---|
| Assess preliminary anti-tumor activity of AZD2284. | — |
Countries
South Africa
Contacts
Public ContactAnson Chan
Project Leader
Outcome results
None listed