Advanced Solid Malignancies
Conditions
Keywords
AZD1390, Malignancies, Solid tumor, Glioblastoma, Radioactivity / radiation, Metabolite / metabolism, ATM kinase inhibitor, Pharmacokinetics, Single-dose, ADME
Brief summary
This is a Phase I, multicentre, single-dose, open-label study to assess the absorption, distribution, metabolism, and excretion of \[14C\]-AZD1390.
Detailed description
On Day 1, participants will receive one dose of \[14C\]-AZD1390 . Participants will be confined to the study site until Day 8. Approximately 8 enrolled male and female participants will receive study intervention in order to achieve a minimum of 4 evaluable participants. Participants in this study will contribute to essential knowledge that will support the development of AZD1390 as a potential treatment for GBM, a malignancy of high unmet need, while being exposed to a low level of immediate risk.
Interventions
DRUGAZD1390
single dose
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Participants with Histologically or cytologically documented, locally advanced or metastatic solid tumour, excluding lymphoma, no active anticancer treatment, * ECOG performance status of 0 or 1 with no deterioration over the 2 weeks, * Predicted life expectancy ≥ 12 weeks, * Adequate organ and marrow function, * Creatinine clearance ≥ 50 mL/min, * Regular bowel movements, * No cancer-associated cachexia (weight loss).
Exclusion criteria
* History or presence of myopathy or raised CK \> 5 × ULN at screening, * History of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, * History or presence of clinically significant hepatic disease, * History of epileptic disorder or any seizure history unrelated to tumour, * History of MDS/AML or with features suggestive of MDS/AML, * Predisposition to bleeding * History of persisting (\> 2 weeks) severe cytopenia * Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection * History of another primary malignancy * Persistent toxicities (CTCAE Grade ≥ 2), excluding alopecia, caused by previous anticancer therapy, * Spinal cord compression or brain metastases for at least 4 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The mass balance of total Radioactivity of AZD1390 and its metabolites after a single oral dose | 6 Weeks | Amount excreted (Ae) (urine) |
| Pharmacokinetic(s) of AZD1390 and the distribution of total radioactivity into blood cells after a single oral dose | 6 weeks | Analysis of plasma: Maximum observed concentration (Cmax) |
| Pharmacokinetic(s) of AZD1390 after a single oral dose | 6 weeks | Analysis of urine: Cumulative amount excreted (CumAe) |
| The distribution of total radioactivity into blood cells after a single oral dose | 6 weeks | Analysis of urine: Fraction (percentage) excreted (Fe) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The phamrmacokinetic(s) of AZD1390 metabolite | 6 weeks | Analysis of plasma: Maximum observed concentration (Cmax) |
| Metabolic profiling following single oral dose of AZD1390 | 6 weeks | Quantification and identification of major metabolites of AZD1390 in plasma and excreta. |
| The safety of a single dose of AZD1390 | 6 weeks | Number of participants with AEs and SAEs and severity of AEs and SAEs (based on CTCAE v5). |
Countries
United Kingdom
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed