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.
Not yet recruiting
Phase 1
| Drug | Synonyms | Arms |
|---|---|---|
| Adavosertib | AZD1775 | Patients with advanced solid tumours |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| 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. |
|
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.
| Maximum Eligible Age: | 130 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Number of patients with serious and non-serious adverse events |
| Time Frame: | From screening to safety follow-up (30 days after last dose) |
| Safety Issue: | |
| Description: | Assessment of the safety and tolerability of adavosertib following oral dosing of the capsule formulation in patients with advanced solid tumours |
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Not yet recruiting |
| Lead Sponsor: | AstraZeneca |
July 2, 2021
