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JOURNAL ONKOLOGIE – STUDIE
ADAGIO

A Study of Adavosertib as Treatment for Uterine Serous Carcinoma

Rekrutierend

NCT-Nummer:
NCT04590248

Studienbeginn:
November 2020

Letztes Update:
01.07.2021

Wirkstoff:
Adavosertib

Indikation (Clinical Trials):
Carcinoma, Cystadenocarcinoma, Serous

Geschlecht:
Frauen

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
AstraZeneca

Collaborator:
Parexel

Studienleiter

Joyce Liu, MD, MPH
Principal Investigator
Dana-Farber Cancer Institute

Kontakt

AstraZeneca Clinical Study Information Center
Kontakt:
Phone: 1-877-240-9479
E-Mail: information.center@astrazeneca.com» Kontaktdaten anzeigen

Studienlocations
(3 von 50)

Research Site
D-13353 Berlin
(Berlin)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
53127 Bonn
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
91054 Erlangen
(Bayern)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
35233 Birmingham
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
60637 Chicago
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
55455 Minneapolis
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
55905 Rochester
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
44109 Cleveland
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
73104 Oklahoma City
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
19301 Paoli
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
19111 Philadelphia
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
84106 Salt Lake City
United StatesZurückgezogen» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

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:

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

Geprüfte Regime

  • Adavosertib (AZD1775):
    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.

Quelle: ClinicalTrials.gov


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