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

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Solid Tumour

Treatments: Drug: Midazolam; Drug: Capivasertib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04958226

D3614C00003

Details and patient eligibility

About

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.

Full 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.

Enrollment: 21 patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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21 participants in 1 patient group

Treatment (Midazolam + Capivasertib)

Experimental group

Description:

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:

Drug: Midazolam

Drug: Capivasertib