Overview

Drug-drug Interaction Study With AZD5305 and Itraconazole in Patients With Advanced Solid Malignancies

Status:
Not yet recruiting
Trial end date:
2023-07-24
Target enrollment:
0
Participant gender:
All
Summary
This study is a single-arm, open-label, multi-centre drug-drug interaction (DDI) study of AZD5305 administered orally in patients with advanced solid tumours.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
AstraZeneca
Treatments:
Itraconazole
Criteria
Inclusion Criteria:

- Provision of signed and dated, written informed consent prior to any study specific
procedures, sampling and analyses.

- Males and females aged ≥ 18 years at the time of screening.

- Patients with documented evidence of locally advanced unresectable or metastatic solid
tumours, excluding lymphoma, who have exhausted standard of care options (or for which
no standard therapies exist) and may be suitable for AZD5305 monotherapy treatment.

- Adequate organ and marrow function.

- An Eastern Cooperative Oncology Group Performance Status (ECOG PS): 0 to 2 with no
deterioration over the previous 2 weeks.

- Life expectancy ≥ 12 weeks.

- Female patients of childbearing potential. Must have a negative pregnancy test result
at screening and prior to each Part of study intervention.

- Female patients must not breastfeed and must not donate or retrieve ova for their own
use from screening to approximately 6 months after the last dose of study
intervention.

Exclusion Criteria:

- Previous enrolment in the present study (ie, dosing with AZD5305 previously initiated
in this study).

- Positive for detection of drugs of abuse or alcohol at screening.

- Concomitant use of medications or herbal supplements known to be cytochrome P450 3A4
enzyme (CYP3A4) substrates, strong, and moderate inhibitors or inducers.

- Using of proton pump inhibitors, histamine H2 receptor antagonists and other antiacid
agents.

- Using of calcium channel blockers.

- Concomitant use of drugs that are known to prolong or shorten QT and have a known risk
of Torsade's de Pointes (TdP).

- During the 4 weeks prior to the first dose, receiving continuous corticosteroids.

- Major surgery within 4 weeks of the first dose of study intervention.

- Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a
limited field of radiation for palliation within 2 weeks of the first dose of study
intervention.

- Treatment with any of the following: any investigational agents or study interventions
from a previous clinical study within 5 half-lives or 3 weeks (whichever is shorter)
of the first dose of study intervention; any other anticancer treatment within the
following time periods prior to the first dose of study intervention: Cytotoxic and
non-cytotoxic treatment: 3 weeks or five half-lives (whichever is shorter); Biological
products including immuno-oncology agents: 4 weeks before enrolment.; any live virus
or bacterial vaccine within 28 days of the first dose of study intervention.

- Any concurrent anticancer therapy or concurrent use of prohibited medications.

- With the exception of alopecia, and peripheral neuropathy; any unresolved toxicities
from prior therapy greater than CTCAE Grade 1.

- Any known history of persisting (> 2 weeks) severe pancytopenia.

- Spinal cord compression, or brain metastases unless asymptomatic and treated and
stable and not requiring continuous corticosteroids at a dose of > 10 mg
prednisone/day or equivalent.

- Any evidence of severe or uncontrolled systemic diseases, including, active bleeding
diatheses, or active infection including hepatitis B, hepatitis C and human
immunodeficiency virus.

- Patients with any known predisposition to bleeding.

- Any of the following cardiac criteria: mean resting QTcF > 450 ms or QTcF < 340 ms
obtained from triplicate ECGs and averaged, recorded within 5 minutes; any factors
that increase the risk of QT prolongation, shortening or risk of arrhythmic events
such as hypokalaemia, congenital long or short QT syndrome, family history of long QT
syndrome, familial short QT syndrome, or unexplained sudden death under 40 years of
age; any clinically important abnormalities in rhythm, conduction or morphology of
resting ECG eg, complete left bundle branch block, second- or third-degree
atrioventricular block, and clinically significant sinus node dysfunction not treated
with pacemaker.

- Other cardiovascular diseases.

- Patients with history of MDS/AML or with features suggestive of MDS/AML.

- Refractory nausea and vomiting, chronic GI diseases, inability to swallow the
formulated product or previous significant bowel resection that would preclude
adequate absorption of AZD5305.

- Known allergy or hypersensitivity to investigational product(s) or any of the
excipients of the investigational product(s).

- Any condition that, in the opinion of the Investigator, would interfere with
evaluation of the study intervention or interpretation of patient safety or study
results.

- Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation
pneumonitis which required steroid treatment, or any evidence of clinically active
ILD.

- Uncontrolled intercurrent illness within the last 12 months.