Testing the Addition of an Anti-cancer Drug, Adavosertib, to Radiation Therapy for Patients With Incurable Esophageal and Gastroesophageal Junction Cancers
A Phase 1 Trial Combining WEE1 Inhibitor Adavosertib (AZD1775) With Radiation Therapy for Metastatic or Inoperable and Ineligible for Definitive Chemoradiation Esophageal and Gastroesophageal Junction Cancer
3 other identifiers
interventional
4
1 country
7
Brief Summary
This phase I trial investigates the side effects and best dose of adavosertib and how well it works when given in combination with radiation therapy in treating patients with esophageal or gastroesophageal junction cancer for which no treatment is currently available (incurable). Adavosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving adavosertib together with radiation therapy kill more tumor cells than radiation therapy alone in treating patients with esophageal and gastroesophageal junction cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Apr 2021
Longer than P75 for phase_1
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 7, 2020
CompletedFirst Posted
Study publicly available on registry
July 8, 2020
CompletedStudy Start
First participant enrolled
April 9, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 29, 2024
CompletedResults Posted
Study results publicly available
June 8, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 18, 2026
ExpectedApril 29, 2026
December 1, 2025
3 years
July 7, 2020
March 28, 2025
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Maximum Tolerated Dose (MTD)
Planned analysis for the MTD was to employ a BOIN design where the target toxicity rate for the MTD is 25% with 75% dose-elimination cut-off. Due to the study ending early and low enrollment numbers, analysis of MTD was unable to be performed. The data presented is the maximum dose that was reached in the dose-escalation.
After completion of treatment, an average of 3 weeks
Number of Adverse Events
Frequency and severity of adverse events and tolerability of the regimen will be collected and summarized with descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
From baseline until completion, an average of 6 months
Secondary Outcomes (5)
Symptom Relief Rate
After completion of treatment, assessed up to 5 years
Time to Second Intervention for Dysphagia
The time from initiation of therapy to the time of second intervention for dysphagia, assessed up to 5 years
Overall Survival
From date of patient enrollment to death due to any cause, an average of 11.5 months
Ogilvie Dysphagia Scores
At baseline and after completion of treatment
Biomarkers
Up to 5 years
Study Arms (1)
Treatment (radiation therapy, adavosertib)
EXPERIMENTALPatients undergo radiation therapy QD 5 days per week for 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive adavosertib PO QD for 2-5 days (depending on dose level) during weeks 1 and 3 of radiation therapy in the absence of disease progression or unacceptable toxicity.
Interventions
Given PO
Undergo radiation therapy
Eligibility Criteria
You may qualify if:
- Patients must have histologically confirmed esophageal cancer (either squamous cell or adenocarcinoma), including Siewert gastroesophageal junction adenocarcinomas types 1 and 2, that is inoperable and not eligible for definitive chemoradiation after multidisciplinary review or have pathologically confirmed or imaging consistent with metastatic disease
- Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of AZD1775 in combination with radiation therapy in patients \< 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky \>= 70%)
- Leukocytes \>= 3,000/mcL
- Absolute neutrophil count \>= 1,500/mcL
- Hemoglobin \>= 9 g/dL
- Platelets \>= 100,000/mcL
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
- Creatinine =\< 1.5 x institutional ULN OR
- Glomerular filtration rate (GFR) \>= 60 mL /min/1.73 m\^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m\^2
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
- Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
- +9 more criteria
You may not qualify if:
- Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to starting study therapy
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
- Patients who are receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD1775
- Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
- Patients with uncontrolled intercurrent illness
- Patients with psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because AZD1775 is a WEE1 inhibiting agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD1775, breastfeeding should be discontinued if the mother is treated with AZD1775. These potential risks may also apply to other agents used in this study
- Prior thoracic or abdominal radiation therapy for cancer that would result in significant overlap of radiation therapy fields at the discretion of the investigator
- Patients with congenital long QT syndrome or with a history of Torsades de pointes unless all risk factors contributed to Torsades have been corrected. AZD1775 has not been studied in patients with ventricular arrhythmias or recent myocardial infarction
- Eligibility of subjects receiving any medications or substances with the potential to affect the activity or pharmacokinetics of AZD1775 will be determined following review by the principal investigator
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
University of Utah Sugarhouse Health Center
Salt Lake City, Utah, 84106, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Eric Miller
- Organization
- The Ohio State University Comprehensive Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Eric D Miller
Ohio State University Comprehensive Cancer Center LAO
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 7, 2020
First Posted
July 8, 2020
Study Start
April 9, 2021
Primary Completion
March 29, 2024
Study Completion (Estimated)
December 18, 2026
Last Updated
April 29, 2026
Results First Posted
June 8, 2025
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.