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Solid TumourPhase 1NCT04958226

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

A Phase 1 study testing Capivasertib and Midazolam in people with Solid Tumour, run by AstraZeneca at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 130 years
Conditions the study is for
Solid Tumour
What is being tested?
Capivasertib and Midazolam
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
5 sitesUnited States
Study dates
15 Oct 2021to 15 Feb 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 130 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.
Show all 9Show fewer
  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Research Site

    Aurora, Colorado, 80045

  • Research Site

    Cleveland, Ohio, 44106

  • Research Site

    Dallas, Texas, 75251

  • Research Site

    Durham, North Carolina, 27710

  • Research Site

    Pittsburgh, Pennsylvania, 15232

Other trials in United States

About this study

Official title: An Open-label, Fixed-sequence Study to Assess the Effect of Repeated Doses of Capivasertib on the Pharmacokinetics of Oral Midazolam (a CYP450 3A Probe) in Patients With Advanced Solid Tumours

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.

Read the 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.

Conditions
Solid Tumour
Being tested
Capivasertib, Midazolam
Keywords
CYP3A inhibitor, Pharmacokinetics, Safety

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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.

Study groups in NCT04958226
Study groupRoleWhat they receive
Treatment (Midazolam + Capivasertib)ExperimentalMidazolam 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.
Receives: Drug: Capivasertib; Drug: Midazolam

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Midazolam AUCinf

    Area under the plasma concentration-time curve from zero to infinity

    Measured: 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)

  2. Midazolam Cmax

    Maximum observed plasma (peak) drug concentration

    Measured: 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)

Secondary outcomes (15)

  1. Midazolam AUClast

    Area under plasma concentration-time curve from zero to the last quantifiable concentration

    Measured: 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)

  2. Midazolam t½λz

    Half-life associated with terminal slope (λz) of a semilogarithmic concentration-time curve

    Measured: 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)

  3. Midazolam tmax

    Time to reach peak or maximum observed concentration

    Measured: 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)

  4. Capivasertib Ctrough

    Observed lowest drug concentration reached before the next dose is administered

    Measured: Cycle 1 Day 9 and Cycle 1 Day 13 (Cycle 1 is 29 days)

  5. Capivasertib Cmax

    Maximum observed plasma (peak) drug concentration

    Measured: Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days)

  6. Capivasertib AUCτ

    Area under plasma concentration-time curve in the dose interval

    Measured: Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days)

  7. Capivasertib t½λz

    Half-life associated with terminal slope (λz) of a semilogarithmic concentration-time curve

    Measured: Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days)

  8. Capivasertib tmax

    Time to reach peak or maximum observed concentration

    Measured: Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days)

  9. Capivasertib CL/F

    Apparent total body clearance of drug from plasma after extravascular administration

    Measured: Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days)

  10. Capivasertib metabolite AZ14102143 Ctrough

    Observed lowest drug concentration reached before the next dose is administered

    Measured: Cycle 1 Day 9 and Cycle 1 Day 13 (Cycle 1 is 29 days)

  11. Capivasertib metabolite AZ14102143 Cmax

    Maximum observed plasma (peak) drug concentration

    Measured: Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days)

  12. Capivasertib metabolite AZ14102143 AUCτ

    Area under plasma concentration-time curve in the dose interval

    Measured: Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days)

  13. Capivasertib metabolite AZ14102143 t½λz

    Half-life associated with terminal slope (λz) of a semilogarithmic concentration-time curve

    Measured: Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days)

  14. Capivasertib metabolite AZ14102143 tmax

    Time to reach peak or maximum observed concentration

    Measured: Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days)

  15. Number of participants with adverse events and serious adverse events

    Assessment of safety and tolerability of capivasertib (with or without the use of standard of care)and in combination with midazolam.

    Measured: From screening to disease progression or discontinuation from the study (up to 15 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jul 2021
  2. Study start15 Oct 2021
  3. Primary completion6 Feb 2023
  4. Study completion15 Feb 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04958226
Sponsor's protocol ID
D3614C00003
Status last verified
Jan 2024
First submitted
1 Jul 2021
Last updated
25 Jan 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Publications

  • Miller C, Sommavilla R, O'Bryant CL, Barve M, Dowlati A, Luke JJ, Khatun M, Morris T, Cullberg M. Pharmacokinetic study of capivasertib and the CYP3A4 substrate midazolam in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2024 Aug;94(2):223-235. doi: 10.1007/s00280-024-04667-3. Epub 2024 Apr 20.

    PubMed 38643311

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Capivasertib and Midazolam in people with Solid Tumour, run by AstraZeneca at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Midazolam AUCinf (time frame: 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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04958226, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2024.

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