Clinical trial NCT04949425: A Study to Assess the Safety and Tolerability of Adavosertib for Patients With Advanced Solid Tumours
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumours
Keywords: Advanced Solid Tumours
Continued Access
Parent Studies
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2021-07-02
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of patients with serious and non-serious adverse events
timeFrame: From screening to safety follow-up (30 days after last dose)
Secondary outcomes:
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
References: