ADAGIO: A Study of Adavosertib as Treatment for Uterine Serous Carcinoma

Sponsor

AstraZeneca (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04590248

Collaborator

Parexel (Industry)

109

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Uterine Serous Carcinoma	Drug: Adavosertib	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

109 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 30, 2020

Anticipated Primary Completion Date :

Sep 30, 2022

Anticipated Study Completion Date :

Sep 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Adavosertib Subjects will receive adavosertib 300 mg administered orally, once daily on Days 1 to 5 and Days 8 to 12 of a 21-day treatment cycle.	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. Other Names: AZD1775

Arm

Intervention/Treatment

Experimental: Adavosertib

Subjects will receive adavosertib 300 mg administered orally, once daily on Days 1 to 5 and Days 8 to 12 of a 21-day treatment cycle.

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.

Other Names:

AZD1775

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) [From baseline to approximately 24 months]
The percentage of subjects with measurable disease at baseline who have a confirmed complete response (CR) or partial response (PR), as determined by Blinded Independent Central Review (BICR) per RECIST v1.1

Secondary Outcome Measures

Duration of response (DoR) [From baseline to approximately 24 months]
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
Depth of response [From baseline to approximately 24 months]
Absolute change and percentage change from baseline will be based on RECIST v1.1 target lesions measurements
Progression free survival (PFS) [From baseline to approximately 24 months]
The time from first dose until the date of objective disease progression or death (by any cause in the absence of progression), derived using RECIST v1.1 assessments based on BICR data
PFS6 [From baseline up to 6 months]
The proportion of subjects alive and progression free at 6 months by Kaplan-Meier estimate
Overall survival (OS) [From baseline to approximately 24 months]
The time from date of first dose until the date of death due to any cause
Disease control rate (DCR) [From baseline to approximately 24 months]
The percentage of subjects who have a best response of confirmed CR or PR or who have stable disease for at least 5 weeks after start of treatment, based on BICR data
Lowest concentration (Ctrough) of adavosertib [Pre-dose (60 minutes prior to dosing) on Day 5 of Cycles 1 and 2 (each cycle is 21 days)]
Lowest plasma concentration of adavosertib before next dose
Maximum concentration (Cmax) of adavosertib [2 hours post-dose on Day 5 of Cycles 1 and 2 (each cycle is 21 days)]
Maximum plasma concentration of adavosertib after oral dosing
Number of subjects with adverse events (AE) and serious AEs [From baseline to post-treatment follow-up (30 days after last dose)]
Assessment of AEs, vital signs, clinical laboratory values, electrocardiogram findings, and AEs leading to dose interruptions, dose reductions, and dose discontinuations

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 130 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects must be aged ≥ 18 years of age inclusive, at the time of signing the informed consent.
Histologically confirmed recurrent or persistent USC. Subjects with carcinosarcomas are not eligible.
Evidence of measurable disease as per RECIST v1.1.
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.
Eastern Cooperative Oncology Group performance (ECOG) status 0-1.
Life expectancy ≥ 12 weeks.
Subjects must have normal organ and marrow function at baseline, within 7 days prior to study drug administration.
Consent to submit and provide a mandatory Formalin-fixed paraffin-embedded tumor sample for central testing.
Female subjects who are not of childbearing potential and women of childbearing potential who agree to use adequate contraceptive measures.

Exclusion Criteria:

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.
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.
Unable to swallow oral medications.
Spinal cord compression or metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.
Subjects with current signs or symptoms of bowel obstruction, including sub-occlusive disease, related to underlying disease.
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

History of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected.
1. Resting corrected QTc interval using the Fridericia formula (QTcF) > 480 msec, or

congenital long QT syndrome.

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

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.
Major surgical procedures ≤ 28 days, or minor surgical procedures ≤ 7 days, prior to beginning study.
Subjects with a known hypersensitivity or contraindication to adavosertib or any of the excipients of the product.
Currently pregnant or breast-feeding.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Burbank	California	United States	91505
2	Research Site	Duarte	California	United States	91010
3	Research Site	La Jolla	California	United States	92093
4	Research Site	West Hollywood	California	United States	90048
5	Research Site	Aurora	Colorado	United States	80045
6	Research Site	Iowa City	Iowa	United States	52242
7	Research Site	Covington	Louisiana	United States	70433
8	Research Site	Boston	Massachusetts	United States	02215
9	Research Site	Rochester	Minnesota	United States	55905
10	Research Site	New Brunswick	New Jersey	United States	08903
11	Research Site	Bronx	New York	United States	10467
12	Research Site	New York	New York	United States	10065
13	Research Site	Spokane	Washington	United States	99202
14	Research Site	Vancouver	Washington	United States	98684
15	Research Site	Toronto		Canada	M5G 2M9
16	Research Site	Dijon cedex		France	21079
17	Research Site	Marseille		France	13273
18	Research Site	Nice		France	6189
19	Research Site	Pierre Benite		France	69495
20	Research Site	Saint Herblain		France	44805
21	Research Site	Milan		Italy	20141
22	Research Site	Napoli		Italy	80131
23	Research Site	Roma		Italy	00168
24	Research Site	A Coruña		Spain	15009
25	Research Site	Barcelona		Spain	08035
26	Research Site	Barcelona		Spain	08036
27	Research Site	Pozuelo de Alarcón		Spain	28223