Trial Outcomes & Findings for Testing the Addition of an Anti-cancer Drug, Adavosertib, to Radiation Therapy for Patients With Incurable Esophageal and Gastroesophageal Junction Cancers (NCT NCT04460937)

Last Updated: 2025-07-08

Results Overview

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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1

Target enrollment

4 participants

Primary outcome timeframe

After completion of treatment, an average of 3 weeks

Results posted on

2025-07-08

Participant Flow

Participant milestones

Participant milestones
Measure	150mg Adavosertib, Radiation Therapy 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. Adavosertib: Given PO Radiation Therapy: Undergo radiation therapy	200mg Adavosertib, Radiation Therapy 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. Adavosertib: Given PO Radiation Therapy: Undergo radiation therapy
Overall Study STARTED	2	2
Overall Study COMPLETED	2	2
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Testing the Addition of an Anti-cancer Drug, Adavosertib, to Radiation Therapy for Patients With Incurable Esophageal and Gastroesophageal Junction Cancers

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: After completion of treatment, an average of 3 weeks

Outcome measures

Outcome measures
Measure	All Participants n=4 Participants 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. Adavosertib: Given PO Radiation Therapy: Undergo radiation therapy	200mg Adavosertib, Radiation Therapy 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. Adavosertib: Given PO Radiation Therapy: Undergo radiation therapy
Maximum Tolerated Dose (MTD)	200 milligrams	—

PRIMARY outcome

Timeframe: From baseline until completion, an average of 6 months

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.

Outcome measures

Outcome measures
Measure	All Participants n=2 Participants 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. Adavosertib: Given PO Radiation Therapy: Undergo radiation therapy	200mg Adavosertib, Radiation Therapy n=2 Participants 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. Adavosertib: Given PO Radiation Therapy: Undergo radiation therapy
Number of Adverse Events Weight loss (Grade 1)	2 Number of Events	3 Number of Events
Number of Adverse Events Weight loss (Grade 2)	0 Number of Events	1 Number of Events
Number of Adverse Events Lymphocyte Count Decreased (Grade 1)	2 Number of Events	1 Number of Events
Number of Adverse Events Lymphocyte Count Decreased (Grade 2)	1 Number of Events	2 Number of Events
Number of Adverse Events Lymphocyte Count Decreased (Grade 3)	1 Number of Events	2 Number of Events
Number of Adverse Events Lymphocyte Count Decreased (Grade 4)	1 Number of Events	0 Number of Events
Number of Adverse Events Trichomonas (Grade 2)	1 Number of Events	0 Number of Events
Number of Adverse Events Back Pain (Grade 1)	0 Number of Events	1 Number of Events
Number of Adverse Events Back Pain (Grade 2)	1 Number of Events	1 Number of Events
Number of Adverse Events Bronchpneumonia (Grade 2)	1 Number of Events	0 Number of Events
Number of Adverse Events Fatigue (Grade 1)	1 Number of Events	0 Number of Events
Number of Adverse Events Fatigue (Grade 2)	1 Number of Events	0 Number of Events
Number of Adverse Events Productive Cough (Grade 1)	1 Number of Events	0 Number of Events
Number of Adverse Events Productive Cough (Grade 2)	1 Number of Events	1 Number of Events
Number of Adverse Events Nausea (Grade 1)	2 Number of Events	0 Number of Events
Number of Adverse Events Nausea (Grade 2)	1 Number of Events	0 Number of Events
Number of Adverse Events Pericardial Effusion (Grade 2)	1 Number of Events	0 Number of Events
Number of Adverse Events Increasing Esophageal Pain (Grade 2)	0 Number of Events	1 Number of Events
Number of Adverse Events Confusion (Grade 1)	0 Number of Events	1 Number of Events
Number of Adverse Events Confusion (Grade 2)	0 Number of Events	1 Number of Events
Number of Adverse Events Hyperglycemia (Grade 1)	1 Number of Events	1 Number of Events
Number of Adverse Events Hyperglycemia (Grade 2)	0 Number of Events	1 Number of Events
Number of Adverse Events Anorexia (Grade 1)	1 Number of Events	1 Number of Events
Number of Adverse Events Anorexia (Grade 2)	0 Number of Events	1 Number of Events
Number of Adverse Events Anemia (Grade 1)	1 Number of Events	1 Number of Events
Number of Adverse Events Anemia (Grade 2)	0 Number of Events	1 Number of Events
Number of Adverse Events Hypoalbuminemia (Grade 1)	3 Number of Events	3 Number of Events
Number of Adverse Events Hypoalbuminemia (Grade 2)	0 Number of Events	1 Number of Events
Number of Adverse Events Dyspnea (Grade 1)	1 Number of Events	1 Number of Events
Number of Adverse Events Dyspnea (Grade 2)	0 Number of Events	1 Number of Events
Number of Adverse Events Sacral Pressure Ulcer (Grade 2)	0 Number of Events	1 Number of Events
Number of Adverse Events Abdominal Pain (Grade 1)	1 Number of Events	1 Number of Events
Number of Adverse Events Abdominal Pain (Grade 2)	0 Number of Events	1 Number of Events
Number of Adverse Events Pneumonitis (Grade 2)	0 Number of Events	1 Number of Events
Number of Adverse Events Alkaline Phosphate Increased (Grade 1)	0 Number of Events	1 Number of Events
Number of Adverse Events Alkaline Phosphate Increased (Grade 2)	0 Number of Events	1 Number of Events
Number of Adverse Events Vomiting (Grade 1)	3 Number of Events	3 Number of Events
Number of Adverse Events Hypoglycemia (Grade 1)	1 Number of Events	0 Number of Events
Number of Adverse Events Urinary Urgency (Grade 1)	1 Number of Events	0 Number of Events
Number of Adverse Events Hematuria (Grade 1)	1 Number of Events	0 Number of Events
Number of Adverse Events Cough (Grade 1)	1 Number of Events	1 Number of Events
Number of Adverse Events Alanine Aminotransferase Increased (Grade 1)	1 Number of Events	0 Number of Events
Number of Adverse Events Bilateral Nipple Pain (Grade 1)	1 Number of Events	0 Number of Events
Number of Adverse Events Bilateral Breast Pain (Grade 1)	1 Number of Events	0 Number of Events
Number of Adverse Events Diarrhea (Grade 1)	1 Number of Events	0 Number of Events
Number of Adverse Events Pain - Right Serratus Anterior Area (Grade 1)	1 Number of Events	0 Number of Events
Number of Adverse Events Esophagitis (Grade 1)	1 Number of Events	0 Number of Events
Number of Adverse Events Nasal Congestion (Grade 1)	1 Number of Events	1 Number of Events
Number of Adverse Events Hypocalcemia (Grade 1)	0 Number of Events	4 Number of Events
Number of Adverse Events Neck Pain (Grade 1)	0 Number of Events	1 Number of Events
Number of Adverse Events Dermatitis Radiation (Grade 1)	0 Number of Events	1 Number of Events
Number of Adverse Events Dizziness (Grade 1)	0 Number of Events	1 Number of Events
Number of Adverse Events Hypotension (Grade 1)	0 Number of Events	1 Number of Events
Number of Adverse Events Aspartate Aminotransferase Increased (Grade 1)	0 Number of Events	1 Number of Events
Number of Adverse Events Blood Lactate Dehydrogenase Increased (Grade 1)	0 Number of Events	1 Number of Events

SECONDARY outcome

Timeframe: After completion of treatment, assessed up to 5 years

Population: Symptom relief data was not measured. Due to low enrollment numbers in phase I and the study not reaching the expansion cohort phase, the study did not collect symptom relief data from participants.

Will be calculated with 95% binomial confidence intervals.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: The time from initiation of therapy to the time of second intervention for dysphagia, assessed up to 5 years

Population: Data was not collected. Data collection was planned for participants in the expansion cohort, and due to the study drug becoming unavailable, the study did not reach the expansion cohort phase. There are no plans for the expansion cohort to be opened at a later date.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From date of patient enrollment to death due to any cause, an average of 11.5 months

Overall survival was planned to be analyzed using Kaplan-Meier methods, resulting in median survival times with 95% confidence interval (CI). Due to early termination of the study and low enrollment numbers, planned analysis did not occur. The data presented in this table is the actual months of survival for each participant, measured from enrollment to death.

Outcome measures

Outcome measures
Measure	All Participants n=4 Participants 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. Adavosertib: Given PO Radiation Therapy: Undergo radiation therapy	200mg Adavosertib, Radiation Therapy 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. Adavosertib: Given PO Radiation Therapy: Undergo radiation therapy
Overall Survival Participant 1	28.7 months	—
Overall Survival Participant 2	5.07 months	—
Overall Survival Participant 3	5.27 months	—
Overall Survival Participant 4	8.0 months	—

SECONDARY outcome

Timeframe: At baseline and after completion of treatment

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 5 years

Population: Biomarkers were not measured. Due to low enrollment numbers in phase I and the study not reaching the expansion cohort phase, the study did not collect biomarker data from participants.

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.

Outcome measures

Outcome data not reported

Adverse Events

150mg Adavosertib, Radiation Therapy

Serious events: 0 serious events

Other events: 2 other events

Deaths: 2 deaths

200mg Adavosertib, Radiation Therapy

Serious events: 0 serious events

Other events: 2 other events

Deaths: 2 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Eric Miller

The Ohio State University Comprehensive Cancer Center

Phone: 614-293-8595

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	150mg Adavosertib, Radiation Therapy n=2 Participants 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. Adavosertib: Given PO Radiation Therapy: Undergo radiation therapy	200mg Adavosertib, Radiation Therapy n=2 Participants 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. Adavosertib: Given PO Radiation Therapy: Undergo radiation therapy	Total n=4 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants

Measure	150mg Adavosertib, Radiation Therapy n=2 participants at risk 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. Adavosertib: Given PO Radiation Therapy: Undergo radiation therapy	200mg Adavosertib, Radiation Therapy n=2 participants at risk 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. Adavosertib: Given PO Radiation Therapy: Undergo radiation therapy
Investigations Weight Loss	100.0% 2/2 • Number of events 2 • From study start until completion, an average of 6 months	100.0% 2/2 • Number of events 4 • From study start until completion, an average of 6 months
Gastrointestinal disorders Vomiting	100.0% 2/2 • Number of events 3 • From study start until completion, an average of 6 months	100.0% 2/2 • Number of events 3 • From study start until completion, an average of 6 months
Gastrointestinal disorders Nausea	100.0% 2/2 • Number of events 3 • From study start until completion, an average of 6 months	0.00% 0/2 • From study start until completion, an average of 6 months
General disorders Fatigue	100.0% 2/2 • Number of events 2 • From study start until completion, an average of 6 months	0.00% 0/2 • From study start until completion, an average of 6 months
Investigations Lymphocyte Count Decreased	100.0% 2/2 • Number of events 5 • From study start until completion, an average of 6 months	100.0% 2/2 • Number of events 5 • From study start until completion, an average of 6 months
Metabolism and nutrition disorders Hyperglycemia	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	100.0% 2/2 • Number of events 2 • From study start until completion, an average of 6 months
Metabolism and nutrition disorders Hypoglycemia	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	0.00% 0/2 • From study start until completion, an average of 6 months
Infections and infestations Trichomonas	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	0.00% 0/2 • From study start until completion, an average of 6 months
Musculoskeletal and connective tissue disorders Back Pain	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	50.0% 1/2 • Number of events 2 • From study start until completion, an average of 6 months
Renal and urinary disorders Urinary Urgency	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	0.00% 0/2 • From study start until completion, an average of 6 months
Blood and lymphatic system disorders Anemia	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	100.0% 2/2 • Number of events 2 • From study start until completion, an average of 6 months
Renal and urinary disorders Hematuria	50.0% 1/2 • Number of events 2 • From study start until completion, an average of 6 months	0.00% 0/2 • From study start until completion, an average of 6 months
Metabolism and nutrition disorders Hypoalbuminemia	100.0% 2/2 • Number of events 3 • From study start until completion, an average of 6 months	100.0% 2/2 • Number of events 4 • From study start until completion, an average of 6 months
Respiratory, thoracic and mediastinal disorders Cough	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months
Investigations Alanine Aminotransferase increased	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	0.00% 0/2 • From study start until completion, an average of 6 months
Gastrointestinal disorders Abdominal Pain	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	50.0% 1/2 • Number of events 2 • From study start until completion, an average of 6 months
Respiratory, thoracic and mediastinal disorders Dyspnea	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	50.0% 1/2 • Number of events 2 • From study start until completion, an average of 6 months
Reproductive system and breast disorders Bilateral Nipple Pain	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	0.00% 0/2 • From study start until completion, an average of 6 months
Reproductive system and breast disorders Breast Pain (bilateral)	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	0.00% 0/2 • From study start until completion, an average of 6 months
Gastrointestinal disorders Diarrhea	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	0.00% 0/2 • From study start until completion, an average of 6 months
Respiratory, thoracic and mediastinal disorders Productive Cough	50.0% 1/2 • Number of events 2 • From study start until completion, an average of 6 months	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months
Musculoskeletal and connective tissue disorders Pain - Right Serratus anterior area	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	0.00% 0/2 • From study start until completion, an average of 6 months
Gastrointestinal disorders Esophagitis	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	0.00% 0/2 • From study start until completion, an average of 6 months
Metabolism and nutrition disorders Anorexia	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	100.0% 2/2 • Number of events 2 • From study start until completion, an average of 6 months
Infections and infestations Bronchpneumonia	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	0.00% 0/2 • From study start until completion, an average of 6 months
Respiratory, thoracic and mediastinal disorders Nasal Congestion	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	100.0% 2/2 • Number of events 2 • From study start until completion, an average of 6 months
Cardiac disorders Pericardial Effusion	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months	0.00% 0/2 • From study start until completion, an average of 6 months
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/2 • From study start until completion, an average of 6 months	100.0% 2/2 • Number of events 4 • From study start until completion, an average of 6 months
Gastrointestinal disorders Increasing Esophageal Pain	0.00% 0/2 • From study start until completion, an average of 6 months	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months
Psychiatric disorders Confusion	0.00% 0/2 • From study start until completion, an average of 6 months	50.0% 1/2 • Number of events 2 • From study start until completion, an average of 6 months
Musculoskeletal and connective tissue disorders Neck Pain	0.00% 0/2 • From study start until completion, an average of 6 months	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months
Injury, poisoning and procedural complications Dermatitis Radiation	0.00% 0/2 • From study start until completion, an average of 6 months	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months
Skin and subcutaneous tissue disorders Sacral pressure ulcer	0.00% 0/2 • From study start until completion, an average of 6 months	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months
Nervous system disorders Dizziness	0.00% 0/2 • From study start until completion, an average of 6 months	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months
Vascular disorders Hypotension	0.00% 0/2 • From study start until completion, an average of 6 months	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/2 • From study start until completion, an average of 6 months	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months
Investigations Aspartate Aminotransferase Increased	0.00% 0/2 • From study start until completion, an average of 6 months	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months
Investigations Alkaline Phosphate Increased	0.00% 0/2 • From study start until completion, an average of 6 months	50.0% 1/2 • Number of events 2 • From study start until completion, an average of 6 months
Investigations Blood lactate dehydrogenase increased	0.00% 0/2 • From study start until completion, an average of 6 months	50.0% 1/2 • Number of events 1 • From study start until completion, an average of 6 months