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A Study of Adavosertib as Treatment for Uterine Serous Carcinoma (ADAGIO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04590248
Recruitment Status : Recruiting
First Posted : October 19, 2020
Last Update Posted : September 10, 2021
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
AstraZeneca

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 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 : November 30, 2020
Estimated Primary Completion Date : November 18, 2022
Estimated Study Completion Date : November 18, 2022

Resource links provided by the National Library of Medicine


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 Name: AZD1775




Primary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 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 :
  1. Duration of response (DoR) [ Time Frame: 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

  2. Depth of response [ Time Frame: From baseline to approximately 24 months ]
    Absolute change and percentage change from baseline will be based on RECIST v1.1 target lesions measurements

  3. Progression free survival (PFS) [ Time Frame: 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

  4. PFS6 [ Time Frame: From baseline up to 6 months ]
    The proportion of subjects alive and progression free at 6 months by Kaplan-Meier estimate

  5. Overall survival (OS) [ Time Frame: From baseline to approximately 24 months ]
    The time from date of first dose until the date of death due to any cause

  6. Disease control rate (DCR) [ Time Frame: 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

  7. Lowest concentration (Ctrough) of adavosertib [ Time Frame: 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

  8. Maximum concentration (Cmax) of adavosertib [ Time Frame: 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

  9. Number of subjects with adverse events (AE) and serious AEs [ Time Frame: 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04590248


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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United States, Alabama
Research Site Not yet recruiting
Birmingham, Alabama, United States, 35233
United States, California
Research Site Recruiting
Burbank, California, United States, 91505
Research Site Recruiting
Duarte, California, United States, 91010
Research Site Recruiting
La Jolla, California, United States, 92093
Research Site Recruiting
West Hollywood, California, United States, 90048
United States, Colorado
Research Site Recruiting
Aurora, Colorado, United States, 80045
United States, Illinois
Research Site Not yet recruiting
Chicago, Illinois, United States, 60637
United States, Iowa
Research Site Recruiting
Iowa City, Iowa, United States, 52242
United States, Louisiana
Research Site Recruiting
Covington, Louisiana, United States, 70433
United States, Massachusetts
Research Site Recruiting
Boston, Massachusetts, United States, 02215
United States, Minnesota
Research Site Not yet recruiting
Minneapolis, Minnesota, United States, 55455
Research Site Recruiting
Rochester, Minnesota, United States, 55905
United States, New Jersey
Research Site Recruiting
New Brunswick, New Jersey, United States, 08903
United States, New York
Research Site Recruiting
Bronx, New York, United States, 10467
Research Site Recruiting
New York, New York, United States, 10065
United States, Ohio
Research Site Not yet recruiting
Cleveland, Ohio, United States, 44109
United States, Oklahoma
Research Site Not yet recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Research Site Not yet recruiting
Paoli, Pennsylvania, United States, 19301
Research Site Not yet recruiting
Philadelphia, Pennsylvania, United States, 19111
United States, Washington
Research Site Recruiting
Spokane, Washington, United States, 99202
Research Site Recruiting
Vancouver, Washington, United States, 98684
Canada, Quebec
Research Site Not yet recruiting
Montreal, Quebec, Canada, H4A 3J1
Canada
Research Site Not yet recruiting
Toronto, Canada, M5G 2M9
France
Research Site Recruiting
Dijon cedex, France, 21079
Research Site Recruiting
Marseille, France, 13273
Research Site Recruiting
Nice, France, 6189
Research Site Recruiting
Pierre Benite, France, 69495
Research Site Recruiting
Saint Herblain, France, 44805
Germany
Research Site Not yet recruiting
Berlin, Germany, D-13353
Research Site Not yet recruiting
Bonn, Germany, 53127
Research Site Not yet recruiting
Erlangen, Germany, 91054
Italy
Research Site Not yet recruiting
Bologna, Italy, 40138
Research Site Not yet recruiting
Candiolo, Italy, 10060
Research Site Not yet recruiting
Catania, Italy, 95100
Research Site Not yet recruiting
Lecce, Italy, 73100
Research Site Recruiting
Milan, Italy, 20141
Research Site Not yet recruiting
Napoli, Italy, 80131
Research Site Not yet recruiting
Roma, Italy, 00168
Spain
Research Site Recruiting
A Coruña, Spain, 15009
Research Site Recruiting
Barcelona, Spain, 08035
Research Site Recruiting
Barcelona, Spain, 08036
Research Site Recruiting
Madrid, Spain, 28040
Research Site Recruiting
Pozuelo de Alarcón, Spain, 28223
Sponsors and Collaborators
AstraZeneca
Parexel
Investigators
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Principal Investigator: Joyce Liu, MD, MPH Dana-Farber Cancer Institute
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04590248    
Other Study ID Numbers: D601HC00002
First Posted: October 19, 2020    Key Record Dates
Last Update Posted: September 10, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame:

AstraZeneca will meet or exceed data availability as per the commitments made to the European Federation of Pharmaceutical Industries and Associations Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Access Criteria:

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Adavosertib
Phase 2b
open-label
single-arm
Additional relevant MeSH terms:
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Carcinoma
Cystadenocarcinoma, Serous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Cystadenocarcinoma
Adenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
MK-1775
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action