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

NCT04949425 | Terminated Phase 1 FDA Drug

• 1 other identifier: D601HC00009
• Study Type: interventional
• Target: 3
• Locations: 2 countries
• Sites: 2

Brief 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

Conditions

Advanced Solid Tumours

Keywords

Advanced Solid Tumours; Continued Access; Parent Studies

Outcome Measures

Primary Outcomes (1)

• 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)

Study Arms (1)

Patients with advanced solid tumours

EXPERIMENTAL

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

Interventions

Adavosertib DRUG

Patients will receive Adavosertib orally.

Also known as: AZD1775

Patients with advanced solid tumours

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Participant has completed one of the parent adavosertib clinical pharmacology studies (i.e., D601HC00004, D601HC00006) and is suitable for continued treatment with adavosertib.
• Eastern Cooperative Oncology Group performance status score of 0 to 1.
• Life expectancy ≥ 12 weeks.
• Participants must have normal organ and marrow function at baseline, within 7 days prior to study drug administration.
• Males and females of childbearing potential who agree to use contraceptive measures should be consistent with clinical study protocol.

You may not qualify if:

• 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 adavosertib.
• Any significant cardiac diseases currently or within the last 6 months such as:
• unstable angina pectoris
• acute myocardial infarction, congestive heart failure
• 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 vaccines are permitted.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (2)

Research Site

Dallas, Texas, 75230, United States

Location

Research Site

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Interventions

adavosertib

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2021
• First Posted: July 2, 2021
• Study Start: September 13, 2021
• Primary Completion: April 21, 2022
• Study Completion: April 21, 2022
• Last Updated: September 2, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share
• 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
• 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

Locations

GB (1); US (1)