A Study to Assess the Safety and Tolerability of Adavosertib for Patients With Advanced Solid Tumours

Advanced Solid Tumours Clinical Trial

Official title:

An Open-label, Non-randomised, Multicentre Study to Allow Continued Access to and Assess the Safety and Tolerability of Adavosertib for Patients With Advanced Solid Tumours Enrolled in Adavosertib Clinical Pharmacology Studies

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04949425
• Other study ID #: D601HC00009
• Status: Terminated
• Phase: Phase 1
• Start date: September 13, 2021
• Est. completion date: April 21, 2022

Study information

• Verified date: August 2022
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to allow continued adavosertib treatment of patients with advanced solid tumours participating in the adavosertib clinical pharmacology studies and to assess the continued safety and tolerability of adavosertib for patients enrolled in adavosertib clinical pharmacology studies (hereafter referred to as the 'parent studies') who continue to use the therapy

Description:

Patients will be screened within 14 days of Day 1 of the treatment period. During screening, patients will undergo an appropriate washout period after the last dose of adavosertib in the parent clinical pharmacology study before receiving the first dose of adavosertib in this study. Patients will continue to receive adavosertib as long as they are benefiting from treatment in the investigator's opinion and do not meet any other discontinuation criteria. The number of patients who enroll is dependent on the number of patients who complete the parent studies, and who tolerate adavosertib in the parent study. The anticipated total duration of the study is approximately 3 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: April 21, 2022
• Est. primary completion date: April 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

1. 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.

2. Participant has completed one of the parent adavosertib clinical pharmacology studies (i.e., D601HC00004, D601HC00006) and is suitable for continued treatment with adavosertib.

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

4. Life expectancy = 12 weeks.

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

6. Males and females of childbearing potential who agree to use contraceptive measures should be consistent with clinical study protocol.

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 adavosertib.

3. 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

4. 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.

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

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

7. 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.

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

9. 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.

10. 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.

11. 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 vaccines are permitted.

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

Related Conditions & MeSH terms

• Advanced Solid Tumours
• Neoplasms

Intervention

Drug:
• Adavosertib
Patients will receive Adavosertib orally.

Locations

Country	Name	City	State
United Kingdom	Research Site	Manchester
United States	Research Site	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with serious and non-serious adverse events	Assessment of the safety and tolerability of adavosertib following oral dosing of the capsule formulation in patients with advanced solid tumours	From screening to safety follow-up (30 days after last dose)