Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04958226
Recruitment Status : Recruiting
First Posted : July 12, 2021
Last Update Posted : July 21, 2022
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Solid Tumour Drug: Capivasertib Drug: Midazolam Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 29 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 15, 2021
Estimated Primary Completion Date : May 26, 2023
Estimated Study Completion Date : May 26, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (Midazolam + 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.
Drug: Capivasertib
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.

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




Primary Outcome Measures :
  1. 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) ]
    Area under the plasma concentration-time curve from zero to infinity

  2. Midazolam Cmax [ 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) ]
    Maximum observed plasma (peak) drug concentration


Secondary Outcome Measures :
  1. Midazolam AUClast [ 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) ]
    Area under plasma concentration-time curve from zero to the last quantifiable concentration

  2. Midazolam t½λz [ 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) ]
    Half-life associated with terminal slope (λz) of a semilogarithmic concentration-time curve

  3. Midazolam tmax [ 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) ]
    Time to reach peak or maximum observed concentration

  4. Capivasertib Ctrough [ Time Frame: 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

  5. Capivasertib Cmax [ Time Frame: Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) ]
    Maximum observed plasma (peak) drug concentration

  6. Capivasertib AUCτ [ Time Frame: Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) ]
    Area under plasma concentration-time curve in the dose interval

  7. Capivasertib t½λz [ Time Frame: 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

  8. Capivasertib tmax [ Time Frame: Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) ]
    Time to reach peak or maximum observed concentration

  9. Capivasertib CL/F [ Time Frame: 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

  10. Capivasertib metabolite AZ14102143 Ctrough [ Time Frame: 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

  11. Capivasertib metabolite AZ14102143 Cmax [ Time Frame: Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) ]
    Maximum observed plasma (peak) drug concentration

  12. Capivasertib metabolite AZ14102143 AUCτ [ Time Frame: Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) ]
    Area under plasma concentration-time curve in the dose interval

  13. Capivasertib metabolite AZ14102143 t½λz [ Time Frame: 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

  14. Capivasertib metabolite AZ14102143 tmax [ Time Frame: Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days) ]
    Time to reach peak or maximum observed concentration

  15. Number of participants with adverse events and serious adverse events [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04958226


Contacts
Layout table for location contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
Layout table for location information
United States, California
Research Site Withdrawn
West Hollywood, California, United States, 90048
United States, Colorado
Research Site Recruiting
Aurora, Colorado, United States, 80045
United States, Maryland
Research Site Withdrawn
Baltimore, Maryland, United States, 21201
United States, Mississippi
Research Site Withdrawn
Jackson, Mississippi, United States, 39213
United States, North Carolina
Research Site Recruiting
Durham, North Carolina, United States, 27710
United States, Ohio
Research Site Withdrawn
Cincinnati, Ohio, United States, 45219
Research Site Recruiting
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Research Site Recruiting
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
Research Site Not yet recruiting
Austin, Texas, United States, 78758
Research Site Recruiting
Dallas, Texas, United States, 75251
Sponsors and Collaborators
AstraZeneca
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04958226    
Other Study ID Numbers: D3614C00003
First Posted: July 12, 2021    Key Record Dates
Last Update Posted: July 21, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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.

Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
CYP3A inhibitor
Pharmacokinetics
Safety
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Midazolam
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action