A study of Adavosertib as Treatment for Uterine Serous Carcinoma
- Conditions
- Recurrent or persistent Uterine Serous Carcinoma (USC) in patients who have previously received at least 1 prior platinum-based chemotherapy regimen for the treatment of USCMedDRA version: 20.0Level: SOCClassification code 10038604Term: Reproductive system and breast disordersSystem Organ Class: 10038604 - Reproductive system and breast disordersMedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000138-16-IT
- Lead Sponsor
- ASTRAZENECA AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 120
1. Capable of giving signed informed consent and has given signed
informed consent as described in Appendix C which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional
genetic research that supports Genomic Initiative.
3. Participant must be aged > = 18 years of age inclusive, at the time of signing the informed consent
4. Histologically confirmed recurrent or persistent USC. For the purposes of this study, participants with endometrial carcinoma of mixed histology where the serous component comprises at least 10% of the tumour will be considered eligible. Participants with carcinosarcomas are not eligible.
5. Evidence of measurable disease as per RECIST v1.1 defined as at least
one lesion, not previously irradiated, that can be accurately measured in at least one dimension (longest diameter to be recorded) as = 10 mm with computed tomography (CT) scan or magnetic resonance imaging (MRI) (except lymph nodes which must have short axis = 15 mm) and which is suitable for accurate repeated measurements.
6. At least 1 prior platinum-based chemotherapy regimen for the management of USC (there is no restriction on the number of prior lines of systemic therapy that a participant may have previously received, and the platinum-based chemotherapy may have been given in the adjuvant setting). Chemotherapy administered only in conjunction with primary radiotherapy as a radiosensitiser should not count as a systemic regimen.
Prior anticancer therapies (IOs, eg, immune checkpoint inhibitors,
vascular endothelial growth factor (VEGF) inhibitors and HER2 targeted therapy) are allowed.
Participants who have known MSI-H or dMMR tumours will not be eligible unless they have already received prior therapy with pembrolizumab or another PD-1/PD-L1 immune checkpoint inhibitor, in territories where this treatment is available for this indication, or are deemed not to be a candidate for immune checkpoint therapy.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
8. Life expectancy = 12 weeks.
9. Participants must have normal organ and marrow function at baseline,
as defined below by laboratory values within 7 days prior to study drug(s) administration:
- Absolute neutrophil count (ANC) >= 1.5 × 10^9 /L
- Haemoglobin (Hb) >= 9 g/dL
- Platelet count >= 100 × 10^9 /L
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
>= 3 x upper limit of normal (ULN) or <= 5 x ULN if known hepatic metastases
- Serum bilirubin within normal limits (WNL) or <=1.5 x ULN in patients
with liver metastases; or total bilirubin = 3.0 x ULN with direct bilirubin
WNL in patients with documented Gilbert's Syndrome
- Serum creatinine <= 1.5 x ULN, or measured creatinine clearance (CrCl)
>= 45 mL/min as estimated using either the Cockcroft-Gault method, a 24-hour urine test or another validated test as per local practice (confirmation of creatinine clearance is only required when creatinine is > 1.5 x institutional ULN).
10. Consent to submit and provide a mandatory FFPE tumour sample for
central testing. The site must confirm that the FFPE sample is available prior to dosing
11. Female patients who are not of childbearing potential and women of
childbearing potential who agree to use adequate contraceptive measures from the time of signing the ICF
1. Any underlying medical condition that would impair the ability of the
participant to receive study treatment, as judged by the investigator.
2. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
3. Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade > 1 toxicity from prior therapy (except alopecia, anorexia or CTCAE grade 2 peripheral neuropathy).
4. Unable to swallow oral medications
5. History of another primary malignancy (exceptions are detailed in Section 5.2 of the Protocol)
6. Spinal cord compression or metastases unless asymptomatic, stable,
and not requiring steroids for at least 4 weeks prior to start of study intervention.
7. Patients with current (or within 28 days prior to Cycle 1, Day 1) signs
or symptoms of bowel obstruction, including sub-occlusive disease, related to underlying disease.
8. Any of the following cardiac diseases currently or within the last 6
months:
- Unstable angina pectoris
- Acute myocardial infarction
- Congestive heart failure >= Class 2 (as defined by New York Heart
Association)
- Conduction abnormality not controlled with pacemaker or medication
- Significant ventricular or supraventricular arrhythmias (patients with
chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible)
9. History of Torsades de pointes unless all risk factors that contributed
to Torsades have been corrected.
10. a) Resting corrected QTc interval using the Fridericia formula (QTcF) > 480 msec (as calculated per institutional standards) obtained from an
electrocardiogram (ECG) (NOTE: if one ECG demonstrates a QTcF > 480 msec, then a mean QTcF of <= 480 msec obtained from 3 ECGs 2-5
minutes apart, is required at study entry), or b) congenital long QT syndrome.
11. Immunocompromised patients, eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV).
12. Patients with known active hepatitis (ie, hepatitis B or C):
- Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible
- Patients positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction is negative for HCV RNA
13. Use of anticancer treatment drug <= 21 days (<= 6 weeks for nitrosoureas or mitomycin C) or use of an investigational product within 5 half-lives prior to the first dose of adavosertib. For PD-1/PD-L1 inhibitors, a minimum of 28 days since last dose is required.
Patients on luteinising-hormone releasing hormone analogue treatment
for more than 6 months are allowed entry into the study and may continue at the discretion of the investigator.
14. Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation or to more than 30% of bone marrow within 4 weeks prior to the first dose of study intervention.
15. Major surgical procedures <= 28 days, or minor surgical procedures <=
7 days, prior to beginning study treatment. No waiting period required following port-a-cath or other central venous access placement.
16. Prior receipt of a cell cycle checkpoint inhibitor (eg, CHK1, WEE1, or ATR inhibition)
17. Has
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method