Human Absorption, Distribution, Metabolism, and Excretion Study of [14C]Adavosertib

NCT ID: NCT05008913

Last Updated: 2022-09-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-01
• Study Completion Date: 2021-11-16

Brief Summary

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.

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

[14C]Adavosertib

Patients will receive a single administration of \[14C\]adavosertib as an oral solution on Day 1.

Group Type: EXPERIMENTAL

[14C]Adavosertib

Intervention Type: DRUG

Patients will receive a single administration of \[14C\]Adavosertib as an oral solution on Day 1.

Interventions

[14C]Adavosertib

Patients will receive a single administration of \[14C\]Adavosertib as an oral solution on Day 1.

Intervention Type: DRUG

Other Intervention Names

AZD1775

Eligibility Criteria

Inclusion Criteria

1. Patient must be ≥ 18 years of age.

2. 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.

3. Eastern Cooperative Oncology Group performance status score of 0 to 1.

4. Life expectancy ≥ 12 weeks.

5. Patients must have normal organ and marrow function at baseline, within 7 days prior to study drug administration.

6. 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.

7. Body weight within 50-100 kg and BMI within the range 18-30 kg/m^2 (inclusive).

8. Regular bowel movements (i.e., on average production of at least 1 faeces per day).

9. Males and females of childbearing potential who agree to use contraceptive measures consistent with local regulations for clinical studies.

Exclusion Criteria

1. Persistent toxicities (Common Terminology Criteria for Adverse Events [CTCAE] Grade > 2) caused by previous anticancer therapy, excluding alopecia and CTCAE Grade 2 peripheral neuropathy.

2. 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.

3. Patients who have participated in another absorption, distribution, metabolism and excretion study within 1 year prior to screening.

4. Any significant cardiac diseases currently or within the last 6 months such as:

1. unstable angina pectoris

2. acute myocardial infarction, congestive heart failure

3. conduction abnormality not controlled with pacemaker or medication

4. significant ventricular or supraventricular arrhythmias

5. 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.

6. Known to have tested positive for human immunodeficiency virus or active tuberculosis infection.

7. Known active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening.

8. 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.

9. Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.

10. 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.

11. 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.

12. 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.

13. Any known hypersensitivity or contraindication to the components of the study intervention adavosertib.

14. Currently pregnant (confirmed with positive pregnancy test) or breast feeding.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Manchester, , United Kingdom

Countries

United Kingdom

Other Identifiers

D601HC00004

Identifier Type: -

Identifier Source: org_study_id