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Neoplasms, Squamous Cell

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Esophageal Diseases

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Adavosertib

Enzyme Inhibitors

Patients 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.

Radiation Therapy

Eric D Miller

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.

PRIMARY OBJECTIVE:

I. To identify the maximally tolerated dose of adavosertib (AZD1775) to be used in combination with radiation therapy for patients with esophageal/gastroesophageal junction (GEJ) cancer that is metastatic or inoperable and not eligible for definitive chemoradiation.

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity. II. To evaluate the efficacy of AZD1775 when administered in combination with radiation therapy by assessing changes in Ogilvie dysphagia score following treatment, time to second intervention for dysphagia, and overall survival.

III. To identify biomarkers that are predictive for response to experimental therapy.

OUTLINE: This is a dose escalation study of adavosertib.

Patients undergo radiation therapy once daily (QD) 5 days per week for 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive adavosertib orally (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.

After completion of study treatment, patients are followed up at 3 weeks, every 3 months for 2 years, then every 6 months for 3 years.

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

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.

Will employ a BOIN design where the target toxicity rate for the MTD is 25% with 75% dose-elimination cut-off.

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.

Will be calculated with 95% binomial confidence intervals.

Patient dysphagia will be evaluated using the Ogilvie dysphagia score, comparing pre-treatment to post-treatment scores

Survival will initially be analyzed using Kaplan-Meier methods, resulting in median survival times with 95% confidence interval (CI).

The scores will be summarized and compared using paired t-test or Wilcoxon signed-rank test. Patient dysphagia will be evaluated using the Ogilvie dysphagia score, comparing pre-treatment to post-treatment scores.

Will be described graphically or summary measures (e.g. mean and standard errors, or median and range) and compared between responders and non-responders using a two sample t-test or Wilcoxon test if the data is not normally distributed.

Spots Global Cancer Trial Database for distal esophagus adenocarcinoma