Advanced Solid TumorsPhase 1ADMENCT05008913
Human Absorption, Distribution, Metabolism, and Excretion Study of [14C]Adavosertib
A Phase 1 study testing [14C]Adavosertib in people with Advanced Solid Tumors, run by AstraZeneca at 1 site in United Kingdom.
Trial summary
This is a non-randomised study in patients with advanced solid malignancies Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- [14C]Adavosertib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Oct 2021to 16 Nov 2021
- 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
- Patient must be ≥ 18 years of age.
- Histologically or cytologically documented, locally advanced or metastatic solid tumour, excluding lymphoma, for which standard therapy does not exist or has proven ineffective or intolerable.
- Eastern Cooperative Oncology Group performance status score of 0 to 1.
- Life expectancy ≥ 12 weeks.
- Patients must have normal organ and marrow function at baseline, within 7 days prior to study drug administration.
- Able and willing to stay in hospital for approximately 9 days (first patient; to be evaluated and possibly adjusted for subsequent patients) for the collection of samples following a single oral dose of [14C]-adavosertib.
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- Body weight within 50-100 kg and BMI within the range 18-30 kg/m^2 (inclusive).
- Regular bowel movements (i.e., on average production of at least 1 faeces per day).
- Males and females of childbearing potential who agree to use contraceptive measures consistent with local regulations for clinical studies.
Who cannot join
- Persistent toxicities (Common Terminology Criteria for Adverse Events [CTCAE] Grade > 2) caused by previous anticancer therapy, excluding alopecia and CTCAE Grade 2 peripheral neuropathy.
- Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of 14C-adavosertib oral solution.
- Patients who have participated in another absorption, distribution, metabolism and excretion study within 1 year prior to screening.
- Any significant cardiac diseases currently or within the last 6 months such as:
- unstable angina pectoris
- acute myocardial infarction, congestive heart failure
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- conduction abnormality not controlled with pacemaker or medication
- significant ventricular or supraventricular arrhythmias
- Any of the following: History or current evidence of congenital long QT syndrome; concomitant medications known to prolong QT interval or history of medication-related QT prolongation.
- Known to have tested positive for human immunodeficiency virus or active tuberculosis infection.
- Known active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening.
- Any evidence of diseases (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant, active infections, and active bleeding diseases) which prohibit participating in the study.
- Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.
- Use of an anti-cancer treatment drug ≤ 21 days (≤ 6 weeks for nitroureas or mitomycin C) or use of an investigational product within 5 half-lives prior to the first dose of adavosertib.
- Patient uses drugs that are sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or are moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued 2 weeks or 5 halflives (whichever is longer) prior to Day 1 of dosing.
- Receipt of live virus and live bacterial vaccines whilst the patient is receiving the study intervention and during the 30-day follow-up period. Inactivated flu vaccines are permitted.
- Any known hypersensitivity or contraindication to the components of the study intervention adavosertib.
- Currently pregnant (confirmed with positive pregnancy test) or breast feeding.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Open-Label, Non-Randomised Study of the Absorption, Distribution, Metabolism, and Excretion of Adavosertib After a Single Oral Dose of [14C]Adavosertib to Patients With Advanced Solid Tumours
This is a non-randomised study in patients with advanced solid malignancies
Read the detailed description
The aim is to recruit approximately 8 patients with a minimum number of 4 pharmacokinetics (PK) evaluable patients.
Each patient will be admitted to the study site pre-dose on Day -1 and will remain at the study site until at least Day 8. Patients will receive a single administration of [14C]adavosertib as an oral solution on Day 1. During this study, whole blood, plasma, urine, faeces, and vomit samples (if presented) will be collected at various time points to characterise the absorption, distribution, metabolism, excretion and PK of adavosertib.
The duration of the residential period will be evaluated following treatment of the first patient and may be adjusted to ensure recovery of at least 90% of the total radioactivity following the dose of [14C]adavosertib and/or until less than 1% of dose is recovered in urine and/or faeces within a 24-hour period.
- Conditions
- Advanced Solid Tumors
- Being tested
- [14C]Adavosertib
- Keywords
- Absorption, Distribution, Metabolism, Excretion, Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[14C]AdavosertibDrug
Also called AZD1775
Patients will receive a single administration of [14C]Adavosertib as an oral solution on Day 1.
| Study group | Role | What they receive |
|---|---|---|
| [14C]Adavosertib | Experimental | Patients will receive a single administration of [14C]adavosertib as an oral solution on Day 1. Receives: Drug: [14C]Adavosertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Amount and cumulative amount excreted and expressed as the percentage of the administered dose into the urine and faeces from time t1 to time t2
Assessment of the mass balance of total radioactivity, including the routes and rates of elimination following a single oral dose [14C]adavosertib.
Measured: Urine and fecal samples collected from pre-dose to 168 hours post-dose
Renal clearance of radioactivity (CLR)
Assessment of renal clearance of adavosertib, including the routes and rates of elimination following a single oral dose [14C]adavosertib.
Measured: From pre-dose to 168 hours post-dose
Maximum observed plasma concentration (Cmax)
Assessment of Cmax of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Measured: From pre-dose to 168 hours post-dose
Area under plasma concentration-time curve from time zero to infinity (AUCinf)
Assessment of AUCinf of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Measured: From pre-dose to 168 hours post-dose
Area under the plasma concentration-time curve from zero to time of last quantifiable concentration (AUClast)
Assessment of AUClast of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Measured: From pre-dose to 168 hours post-dose
Time to reach peak or maximum observed concentration following drug administration (tmax)
Assessment of tmax of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Measured: From pre-dose to 168 hours post-dose
Terminal elimination rate constant (λz)
Assessment of λz of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Measured: From pre-dose to 168 hours post-dose
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz)
Assessment of t½λz of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Measured: From pre-dose to 168 hours post-dose
Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
Assessment of CL/F of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Measured: From pre-dose to 168 hours post-dose
Mean Residence Time of the unchanged drug in the systemic circulation (MRTinf)
Assessment of MRTinf of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Measured: From pre-dose to 168 hours post-dose
Volume of distribution (apparent) at steady state following extravascular administration (Vss/F)
Assessment of Vss/F of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Measured: From pre-dose to 168 hours post-dose
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)
Assessment of Vz/F of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Measured: From pre-dose to 168 hours post-dose
Ratio of AUCinf of plasma adavosertib relative to AUCinf of plasma total radioactivity [AUCinf Plasma:Total Plasma Ratio]
Assessment of AUCinf plasma adavosertib:Total plasma radioactivity ratio following a single oral dose of [14C]adavosertib.
Measured: From pre-dose to 168 hours post-dose
Ratio of AUCinf of whole blood total radioactivity to AUCinf of plasma total radioactivity [AUCinf Blood:Plasma Ratio]
Assessment of AUCinf Blood:Plasma Ratio total radioactivity following a single oral dose of [14C]adavosertib.
Measured: From pre-dose to 168 hours post-dose
Amount, cumulative amount, and cumulative percentage of unchanged adavosertib excreted into urine from time t1 to time t2
Assessment of unchanged adavosertib following a single oral dose of [14C]adavosertib.
Measured: Urine collected from pre-dose to 168 hours post-dose
Renal clearance of adavosertib from plasma (CLR)
Assessment of CLR of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Measured: From pre-dose to 168 hours post-dose
Secondary outcomes (1)
Number of patients with adverse events (AE) and serious AEs (SAE)
Assessment of the safety and tolerability of adavosertib following oral dosing in patients with advanced solid tumours.
Measured: From screening (Day -28 to Day -1) until end of study (within 30 [±7] days of adavosertib dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2021
- Study start1 Oct 2021
- Primary completion16 Nov 2021
- Study completion16 Nov 2021
Why it stopped: Study terminated because the clinical development programme for Adavosertib has been discontinued
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05008913
- Sponsor's protocol ID
- D601HC00004
- Acronym
- ADME
- Status last verified
- Aug 2022
- First submitted
- 10 Aug 2021
- Last updated
- 6 Sep 2022
- 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 requests 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.
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-Label, Non-Randomised Study of the Absorption, Distribution, Metabolism, and Excretion of Adavosertib After a Single Oral Dose of [14C]Adavosertib to Patients With Advanced Solid Tumours
- ClinicalTrials.gov ID
- NCT05008913
- Acronym / sponsor ID
- ADME / D601HC00004
- Conditions
- Advanced Solid Tumors
- Keywords
- Absorption, Distribution, Metabolism, Excretion, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated because the clinical development programme for Adavosertib has been discontinued
- Enrolment
- 2 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 1 Oct 2021 (actual)
- Primary completion
- 16 Nov 2021 (actual)
- Study completion
- 16 Nov 2021 (actual)
- First posted
- 17 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a non-randomised study in patients with advanced solid malignancies
Detailed description
The aim is to recruit approximately 8 patients with a minimum number of 4 pharmacokinetics (PK) evaluable patients.
Each patient will be admitted to the study site pre-dose on Day -1 and will remain at the study site until at least Day 8. Patients will receive a single administration of [14C]adavosertib as an oral solution on Day 1. During this study, whole blood, plasma, urine, faeces, and vomit samples (if presented) will be collected at various time points to characterise the absorption, distribution, metabolism, excretion and PK of adavosertib.
The duration of the residential period will be evaluated following treatment of the first patient and may be adjusted to ensure recovery of at least 90% of the total radioactivity following the dose of [14C]adavosertib and/or until less than 1% of dose is recovered in urine and/or faeces within a 24-hour period.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| [14C]Adavosertib | Experimental | Drug: [14C]AdavosertibPatients will receive a single administration of [14C]adavosertib as an oral solution on Day 1. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patient must be ≥ 18 years of age.
- Histologically or cytologically documented, locally advanced or metastatic solid tumour, excluding lymphoma, for which standard therapy does not exist or has proven ineffective or intolerable.
- Eastern Cooperative Oncology Group performance status score of 0 to 1.
- Life expectancy ≥ 12 weeks.
- Patients must have normal organ and marrow function at baseline, within 7 days prior to study drug administration.
Key exclusion criteria (18 listed)
- Persistent toxicities (Common Terminology Criteria for Adverse Events [CTCAE] Grade > 2) caused by previous anticancer therapy, excluding alopecia and CTCAE Grade 2 peripheral neuropathy.
- Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of 14C-adavosertib oral solution.
- Patients who have participated in another absorption, distribution, metabolism and excretion study within 1 year prior to screening.
- Any significant cardiac diseases currently or within the last 6 months such as:
- Any of the following: History or current evidence of congenital long QT syndrome; concomitant medications known to prolong QT interval or history of medication-related QT prolongation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [14C]AdavosertibAlso: AZD1775Patients will receive a single administration of [14C]Adavosertib as an oral solution on Day 1. | Drug | [14C]Adavosertib |
Primary outcome
Amount and cumulative amount excreted and expressed as the percentage of the administered dose into the urine and faeces from time t1 to time t2
Time frame: Urine and fecal samples collected from pre-dose to 168 hours post-dose
Assessment of the mass balance of total radioactivity, including the routes and rates of elimination following a single oral dose [14C]adavosertib.
Renal clearance of radioactivity (CLR)
Time frame: From pre-dose to 168 hours post-dose
Assessment of renal clearance of adavosertib, including the routes and rates of elimination following a single oral dose [14C]adavosertib.
Maximum observed plasma concentration (Cmax)
Time frame: From pre-dose to 168 hours post-dose
Assessment of Cmax of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Area under plasma concentration-time curve from time zero to infinity (AUCinf)
Time frame: From pre-dose to 168 hours post-dose
Assessment of AUCinf of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Area under the plasma concentration-time curve from zero to time of last quantifiable concentration (AUClast)
Time frame: From pre-dose to 168 hours post-dose
Assessment of AUClast of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Time to reach peak or maximum observed concentration following drug administration (tmax)
Time frame: From pre-dose to 168 hours post-dose
Assessment of tmax of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Terminal elimination rate constant (λz)
Time frame: From pre-dose to 168 hours post-dose
Assessment of λz of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz)
Time frame: From pre-dose to 168 hours post-dose
Assessment of t½λz of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
Time frame: From pre-dose to 168 hours post-dose
Assessment of CL/F of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Mean Residence Time of the unchanged drug in the systemic circulation (MRTinf)
Time frame: From pre-dose to 168 hours post-dose
Assessment of MRTinf of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Volume of distribution (apparent) at steady state following extravascular administration (Vss/F)
Time frame: From pre-dose to 168 hours post-dose
Assessment of Vss/F of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)
Time frame: From pre-dose to 168 hours post-dose
Assessment of Vz/F of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
Ratio of AUCinf of plasma adavosertib relative to AUCinf of plasma total radioactivity [AUCinf Plasma:Total Plasma Ratio]
Time frame: From pre-dose to 168 hours post-dose
Assessment of AUCinf plasma adavosertib:Total plasma radioactivity ratio following a single oral dose of [14C]adavosertib.
Ratio of AUCinf of whole blood total radioactivity to AUCinf of plasma total radioactivity [AUCinf Blood:Plasma Ratio]
Time frame: From pre-dose to 168 hours post-dose
Assessment of AUCinf Blood:Plasma Ratio total radioactivity following a single oral dose of [14C]adavosertib.
Amount, cumulative amount, and cumulative percentage of unchanged adavosertib excreted into urine from time t1 to time t2
Time frame: Urine collected from pre-dose to 168 hours post-dose
Assessment of unchanged adavosertib following a single oral dose of [14C]adavosertib.
Renal clearance of adavosertib from plasma (CLR)
Time frame: From pre-dose to 168 hours post-dose
Assessment of CLR of adavosertib and total radioactivity following a single oral dose of [14C]adavosertib.
1 secondary outcome
Number of patients with adverse events (AE) and serious AEs (SAE)
Time frame: From screening (Day -28 to Day -1) until end of study (within 30 [±7] days of adavosertib dose)
Results and safety
The study was stopped early (reason given: Study terminated because the clinical development programme for Adavosertib has been discontinued). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2022.
- Individual participant dataSharing planned: 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 requests 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing [14C]Adavosertib in people with Advanced Solid Tumors, run by AstraZeneca at 1 site in United Kingdom.
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 9 inclusion and 18 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: stopped early, as of the sponsor's last update on 6 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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 was stopped early (reason given: Study terminated because the clinical development programme for Adavosertib has been discontinued). Results are not available in the source record.
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?
Amount and cumulative amount excreted and expressed as the percentage of the administered dose into the urine and faeces from time t1 to time t2 (time frame: Urine and fecal samples collected from pre-dose to 168 hours post-dose). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Sep 2022.