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

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

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

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumours
• Intervention / Treatment: Drug: Adavosertib

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • Research Site
• United States
  • Texas
    • Dallas, Texas, United States, 75230
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 128 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with advanced solid tumours; Patients with advanced solid tumours will receive Adavosertib once daily for 5 days followed by 2 days off for 2 weeks out of a 21-day cycle.	Drug: Adavosertib; Patients will receive Adavosertib orally.; Other Names: AZD1775

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2021
• Primary Completion (Actual): April 21, 2022
• Study Completion (Actual): April 21, 2022

Study Registration Dates

• First Submitted: June 25, 2021
• First Submitted That Met QC Criteria: June 25, 2021
• First Posted (Actual): July 2, 2021

Study Record Updates

• Last Update Posted (Actual): September 2, 2022
• Last Update Submitted That Met QC Criteria: September 1, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Advanced Solid Tumours; Continued Access; Parent Studies
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Adavosertib
• Other Study ID Numbers: D601HC00009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD 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 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.

• IPD Sharing 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 refer to our disclosure commitment at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the de-identified 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No