A Study to Assess the Effect of Capivasertib on Midazolam in Patients With Advanced Solid Tumours

AstraZeneca21 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Tumour

Interventions

CapivasertibDRUG

Capivasertib (tablet) will be given as an intermittent schedule (4 days on/3 days off) from Cycle 1 Day 2 until discontinuation. Capivasertib will be administrated in both Part A and Part B.

MidazolamDRUG

Single doses of midazolam (syrup, 1 mg) will be given on cycle 1 Days 1, 8, and 12.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 130 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Participants with documented evidence of locally advanced inoperable or metastatic solid tumours who may be suitable to receive capivasertib treatment. 2. Eastern Cooperative Oncology Group/World Health Organization performance status 0 to 1 and with minimum life expectancy for 12 weeks. 3. Participant should have at least one lesion that can be assessed by computed tomography/magnetic resonance imaging or plain X-ray at baseline. 4. Body mass index within the range 18 to 32 kg/m\^2 Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: 1. 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. 2. Participants with diabetes mellitus type I or participants with diabetes mellitus type II requiring insulin treatment. 3. Undergone a major surgery within 4 weeks of the first dose of capivasertib. 4. 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. 5. Participants with spinal cord compression or brain metastases. 6. Participants with severe or uncontrolled systemic diseases, active bleeding diatheses, or active infection. 7. Previous allogeneic bone marrow transplant or solid organ transplant. 8. Known immunodeficiency syndrome.

Locations (5)

Research Site

Aurora, Colorado, United States

Research Site

Durham, North Carolina, United States

Research Site

Cleveland, Ohio, United States

Research Site

Pittsburgh, Pennsylvania, United States