Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal
Conditions
Keywords
CYP3A inhibitor, TOP1 inhibitor payload
Brief summary
The purpose of this study is to assess the effect of itraconazole on the pharmacokinetics (PK) of AZ14170132.
Detailed description
This is a non-randomized, open-label, fixed sequence study to be conducted at multiple study centers. The study will consist of 2 parts: Part A of the study will comprise of: * Screening period * Treatment period: The treatment period will comprise of Cycles 1, 2 and 3 where the participants will receive AZD5335 along with itraconazole * Follow-up visit (not applicable for participants involved in Part B) Part B of the study will comprise of: * Treatment period: Cycle 4 and onwards * Safety Follow-up period
Interventions
DRUGAZD5335
AZD5335 will be administered as IV infusion.
DRUGItraconazole
Itraconazole capsule will be administered orally.
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with Platinum-resistant, relapsed, high- grade epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer and: (a) have received at least 1 prior line of platinum-containing chemotherapy and have progressed on or within 6 months after the date of the last dose of platinum; (b) must have received prior bevacizumab and/or Poly (ADP-ribose) polymerase (PARP) inhibitors according to local guidelines, unless ineligible. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
Exclusion criteria
* Spinal cord compression or a history of leptomeningeal carcinomatosis. * Unresolved toxicities of Grade ≥ 2 (National Cancer Institute-Common Terminology Criteria for Adverse Events v5.0) from prior therapy. * History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required oral or IV steroids or supplemental oxygen, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. * Uncontrolled intercurrent illness within 12 months prior to screening. * Any other contraindication for receiving itraconazole according to the prescribing information and the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under curve from time 0 to time 17 days (AUC0-17days) | Cycle 2 and Cycle 3 (each cycle is of 21 days) | The effect of itraconazole on the pharmacokinetics (PK) of AZ14170132 will be assessed. |
| Maximum plasma drug concentration (Cmax) | Cycle 2 and Cycle 3 (each cycle is of 21 days) | The effect of itraconazole on the PK of AZ14170132 will be assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma drug concentration (Cmax) | Cycle 2 and Cycle 3 (each cycle is of 21 days) | Cmax of AZ14170132 will be assessed. |
| Area under curve from time 0 to time 17 days (AUC0-17days) | Cycle 2 and Cycle 3 (each cycle is of 21 days) | AUC0-17days of AZ14170132 will be assessed. |
| Minimum plasma drug concentration (Cmin) | Cycle 2 and Cycle 3 (each cycle is of 21 days) | Cmin of AZ14170132 will be assessed. |
| Area under curve from time 0 to the time of last measurable concentration (AUC0-t) | Cycle 2 and Cycle 3 (each cycle is of 21 days) | AUC0-t of AZ14170132 will be assessed. |
| Terminal elimination (lambda_z) | Cycle 2 and Cycle 3 (each cycle is of 21 days) | lambda\_z of AZ14170132 will be assessed. |
| Half life (t1/2) | Cycle 2 and Cycle 3 (each cycle is of 21 days) | t1/2 of AZ14170132 will be assessed. |
| Time to maximum observed concentration (tmax) | Cycle 2 and Cycle 3 (each cycle is of 21 days) | tmax of AZ14170132 will be assessed. |
| Number of participants with adverse events (AEs) and serious adverse events (SAEs) | Part A: up to 121 days; Part B: up to 365 days post last participant first dose | The safety and tolerability of AZD5335 alone and in combination with itraconazole will be assessed. |
| Objective response rate (ORR) | Part A: up to 121 days; Part B: up to 365 days post last participant first dose | The ORR is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR), with the denominator defined as the number of participants in the response evaluable set. |
| Duration of response (DoR) | Part A: up to 121 days; Part B: up to 365 days post last participant first dose | The DoR is defined as the time from the date of first documented objective response (which is subsequently confirmed) until date of first documented disease progression or death (by any cause in the absence of disease progression). |
| Progression-free Survival (PFS) | From Day 1 until until disease progression or death (up to 2 years) | The PFS is defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participant withdraws from randomised therapy or receives another anti-cancer therapy prior to progression. |
Countries
Georgia, Ireland, Portugal, Spain
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed