A Study of Adavosertib as Treatment for Uterine Serous Carcinoma

Uterine Serous Carcinoma Clinical Trial

— ADAGIO  

Official title:

A Phase 2b, Open-label, Single-arm, Multi-centre Study Assessing the Efficacy and Safety of Adavosertib as Treatment for Recurrent or Persistent Uterine Serous Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04590248
• Other study ID #: D601HC00002
• Status: Completed
• Phase: Phase 2
• Start date: November 30, 2020
• Est. completion date: February 7, 2023

Study information

• Verified date: August 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase 2b study aims to evaluate the efficacy and safety of adavosertib, an inhibitor of the tyrosine kinase WEE1, in subjects with recurrent or persistent uterine serous carcinoma (USC) who have previously received at least 1 prior platinum-based chemotherapy regimen for the management of USC.

Description:

This Phase 2b, open-label, single-arm, multi-center study will assess the efficacy and safety of adavosertib in eligible subjects with histologically confirmed recurrent or persistent USC, evidence of measurable disease as per Response Evaluation Criteria in Solid Tumors.(RECIST) v1.1, and who have received at least 1 prior platinum-based chemotherapy regimen for the management of USC. Subjects with carcinosarcomas are not eligible.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: February 7, 2023
• Est. primary completion date: May 23, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

1. Subjects must be aged = 18 years of age inclusive, at the time of signing the informed consent.

2. Histologically confirmed recurrent or persistent USC. Subjects with carcinosarcomas are not eligible.

3. Evidence of measurable disease as per RECIST v1.1.

4. At least 1 prior platinum-based chemotherapy regimen for the management of USC. Prior receipt of immune checkpoint inhibitors, vascular endothelial growth factor (VEGF) inhibitors and human epidermal growth factor receptor 2 (HER2) targeted therapy is allowed. There is no restriction on the number of prior lines of systemic therapy.

5. Eastern Cooperative Oncology Group performance (ECOG) status 0-1.

6. Life expectancy = 12 weeks.

7. Subjects must have normal organ and marrow function at baseline, within 7 days prior to study drug administration.

8. Consent to submit and provide a mandatory Formalin-fixed paraffin-embedded tumor sample for central testing.

9. Female subjects who are not of childbearing potential and women of childbearing potential who agree to use adequate contraceptive measures.

Exclusion Criteria:

1. Any underlying medical condition and uncontrolled intercurrent illness that would impair the ability of the subject to receive study treatment, as judged by the investigator.

2. With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment.

3. Unable to swallow oral medications.

4. Spinal cord compression or metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.

5. Subjects with current signs or symptoms of bowel obstruction, including sub-occlusive disease, related to underlying disease.

6. Any of the following cardiac diseases currently or within the last 6 months:

• Unstable angina pectoris

• Acute myocardial infarction

• Congestive heart failure

• Conduction abnormality not controlled with pacemaker or medication

• Significant ventricular or supraventricular arrhythmias

7. History of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected.

8. a) Resting corrected QTc interval using the Fridericia formula (QTcF) > 480 msec, or b) congenital long QT syndrome.

9. Immunocompromised subjects.

10. Subjects with known active hepatitis (ie, hepatitis B or C).

11. Prior treatment with any of the following:

• Cell cycle checkpoint inhibitor.

• 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 Programmed cell death-1 receptor (PD-1) /Programmed death-ligand 1 (PD-L1) inhibitors, a minimum of 28 days since last dose is required.

• Prescription or non-prescription drugs known as moderate to strong inhibitors / inducers of CYP3A4 within 2 weeks prior to the first dose of study treatment.

• Herbal medications 7 days prior to first dose of study treatment.

12. Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation within 4 weeks prior to the first dose of study intervention.

13. Major surgical procedures = 28 days, or minor surgical procedures = 7 days, prior to beginning study.

14. Subjects with a known hypersensitivity or contraindication to adavosertib or any of the excipients of the product.

15. Currently pregnant or breast-feeding.

Related Conditions & MeSH terms

• Carcinoma
• Uterine Serous Carcinoma

Intervention

Drug:
• Adavosertib
The subjects will receive oral adavosertib 300 mg, once daily on Days 1 to 5 and Days 8 to 12 of a 21-day treatment cycle.

Locations

Country	Name	City	State
Canada	Research Site	Toronto
France	Research Site	Dijon cedex
France	Research Site	Marseille
France	Research Site	Nice
France	Research Site	Pierre Benite
France	Research Site	Saint Herblain
Italy	Research Site	Milan
Italy	Research Site	Napoli
Italy	Research Site	Roma
Spain	Research Site	A Coruña
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Pozuelo de Alarcón
United States	Research Site	Aurora	Colorado
United States	Research Site	Boston	Massachusetts
United States	Research Site	Bronx	New York
United States	Research Site	Burbank	California
United States	Research Site	Covington	Louisiana
United States	Research Site	Duarte	California
United States	Research Site	Iowa City	Iowa
United States	Research Site	La Jolla	California
United States	Research Site	New Brunswick	New Jersey
United States	Research Site	New York	New York
United States	Research Site	Rochester	Minnesota
United States	Research Site	Spokane	Washington
United States	Research Site	Vancouver	Washington
United States	Research Site	West Hollywood	California

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Countries where clinical trial is conducted

United States,  Canada,  France,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	Per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 for target lesions (TLs) and assessed by computed tomography (CT) or magnetic resonance imaging (MRI): Complete response (CR), Disappearance of all target lesions; Partial response (PR), >=30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.	up to 75 weeks
Secondary	Duration of Response (DoR)	The time from the date of first documented response until date of documented progression per RECIST v1.1 as assessed by BICR, or death in the absence of disease progression	up to 75 weeks
Secondary	Depth of Response	Depth of response is defined as best percentage change from baseline in target lesion size, which is the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction. A negative change denotes a reduction in target lesion size.	Up to 75 weeks
Secondary	Progression Free Survival (PFS)	The time from first dose until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraws from study drug or receives another anticancer therapy prior to progression. PFS was assessed per RECIST v1.1 using CT or MRI scans by BICR.	Up to 75 weeks
Secondary	Progression Free Survival Rate at 6 Months (PFS6)	The progression free survival rate was assessed at 6 months by Kaplan-Meier estimate per RECIST v1.1.	Up to 6 months
Secondary	Overall Survival (OS)	The time from date of first dose until the date of death due to any cause	Up to 75 weeks
Secondary	Disease Control Rate (DCR)	The percentage of participants who have a best overall response of confirmed response (CR) or partial response (PR) or who have stable disease for at least 5 weeks after start of treatment, based on BICR.	Up to 75 weeks
Secondary	Lowest Concentration (Ctrough) of Adavosertib	Lowest plasma concentration of adavosertib was evaluated as pharmacokinetic paramerter.	Cycle 1, Day 5 and Cycle 2, Day 5 (pre-dose) (each cycle is 21 days)
Secondary	Maximum Concentration (Cmax) of Adavosertib	Maximum plasma concentration of adavosertib was evaluated as pharmacokinetic parameter.	Cycle 1, Day 5 and Cycle 2, Day 5 (2 hours post-dose) (each cycle is 21 days)
Secondary	Number of Participants With Treatment Emergent Adverse Events (AEs)	The number of participants with treatment emergent adverse events (AEs) were assessed as variable of safety and tolerability. The adverse events reported here were treatment emergent.	From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks

External Links

•   CSP
•   D601HC00002_CSR_Synopsis_redacted
•   Statistical Analysis Plan (SAP)