A Study to Assess the Effect of Capivasertib on Midazolam in Patients With Advanced Solid Tumours
- Registration Number
- NCT04958226
- Lead Sponsor
- AstraZeneca
- Brief Summary
This is an open-label, fixed-sequence study to evaluate the effect of capivasertib on the pharmacokinetics (PK) of midazolam, a sensitive CYP3A substrate. The PK of midazolam will be assessed when administered alone and in combination with repeated doses of capivasertib.
- Detailed Description
This is 2 part study: Part A and Part B. Part A of the study consists of a screening period and 3 treatment periods (midazolam alone, capivasertib alone, and midazolam + capivasertib). During Part A, the PK profile of midazolam will be determined with and without capivasertib.All participants will receive capivasertib treatment (4 days on/3 days off); however, at the Investigator's discretion, ER positive breast cancer patients may also receive fulvestrant in addition to capivasertib and midazolam. Participants completing Part A without disease progression or unacceptable toxicity, who are considered likely to continue to benefit from further capivasertib treatment (with or without certain standard of care treatment) in the opinion of the Investigator will enter Part B. Part B of the study consists of an extended treatment period with capivasertib, with or without certain standard of care treatment, followed by a 30-day safety follow-up.
Part A of the study may be extended to allow the administration of midazolam on a rescheduled Cycle 1 Day 8(C1D8) and Cycle 1 Day 12(C1D12 ) visit.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 21
- Participants with documented evidence of locally advanced inoperable or metastatic solid tumours who may be suitable to receive capivasertib treatment.
- Eastern Cooperative Oncology Group/World Health Organization performance status 0 to 1 and with minimum life expectancy for 12 weeks.
- Participant should have at least one lesion that can be assessed by computed tomography/magnetic resonance imaging or plain X-ray at baseline.
- Body mass index within the range 18 to 32 kg/m^2
Participants are excluded from the study if any of the following criteria apply:
- Radiotherapy with a wide field of radiation within 4 weeks of the first dose of capivasertib and/or radiotherapy with a limited field of radiation for palliation within 2 weeks prior to study intervention initiation.
- Participants with diabetes mellitus type I or participants with diabetes mellitus type II requiring insulin treatment.
- Undergone a major surgery within 4 weeks of the first dose of capivasertib.
- Any unresolved toxicities from prior therapies higher than CTCAE grade 2 or any unresolved toxicity that may interfere with PK assessment at the time of study intervention initiation.
- Participants with spinal cord compression or brain metastases.
- Participants with severe or uncontrolled systemic diseases, active bleeding diatheses, or active infection.
- Previous allogeneic bone marrow transplant or solid organ transplant.
- Known immunodeficiency syndrome.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Treatment (Midazolam + Capivasertib) Midazolam Midazolam will be administered on Cycle 1 Day 1 and Cycle 1 Day 8. Capivasertib will be administrated from Cycle 1 Day 2 as an intermittent schedule (4 days on/3 days off) until discontinuation. On Cycle 1 Day 12, Midazolam will be administrated with Capivasertib. Treatment (Midazolam + Capivasertib) Capivasertib Midazolam will be administered on Cycle 1 Day 1 and Cycle 1 Day 8. Capivasertib will be administrated from Cycle 1 Day 2 as an intermittent schedule (4 days on/3 days off) until discontinuation. On Cycle 1 Day 12, Midazolam will be administrated with Capivasertib.
- Primary Outcome Measures
Name Time Method Midazolam AUCinf Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9, Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) Area under the plasma concentration-time curve from zero to infinity
Midazolam Cmax Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9, Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) Maximum observed plasma (peak) drug concentration
- Secondary Outcome Measures
Name Time Method Midazolam AUClast Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9, Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) Area under plasma concentration-time curve from zero to the last quantifiable concentration
Capivasertib Ctrough Cycle 1 Day 9 and Cycle 1 Day 13 (Cycle 1 is 29 days) Observed lowest drug concentration reached before the next dose is administered
Capivasertib AUCτ Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) Area under plasma concentration-time curve in the dose interval
Capivasertib t½λz Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) Half-life associated with terminal slope (λz) of a semilogarithmic concentration-time curve
Capivasertib tmax Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) Time to reach peak or maximum observed concentration
Capivasertib CL/F Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) Apparent total body clearance of drug from plasma after extravascular administration
Capivasertib metabolite AZ14102143 Ctrough Cycle 1 Day 9 and Cycle 1 Day 13 (Cycle 1 is 29 days) Observed lowest drug concentration reached before the next dose is administered
Capivasertib metabolite AZ14102143 Cmax Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) Maximum observed plasma (peak) drug concentration
Capivasertib metabolite AZ14102143 AUCτ Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) Area under plasma concentration-time curve in the dose interval
Capivasertib metabolite AZ14102143 t½λz Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) Half-life associated with terminal slope (λz) of a semilogarithmic concentration-time curve
Capivasertib metabolite AZ14102143 tmax Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) Time to reach peak or maximum observed concentration
Number of participants with adverse events and serious adverse events From screening to disease progression or discontinuation from the study (up to 15 months) Assessment of safety and tolerability of capivasertib (with or without the use of standard of care)and in combination with midazolam.
Midazolam t½λz Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9, Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) Half-life associated with terminal slope (λz) of a semilogarithmic concentration-time curve
Midazolam tmax Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9, Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) Time to reach peak or maximum observed concentration
Capivasertib Cmax Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) Maximum observed plasma (peak) drug concentration
Trial Locations
- Locations (1)
Research Site
🇺🇸Dallas, Texas, United States