Trial Outcomes & Findings for AZD1775 in Treating Patients With Advanced Refractory Solid Tumors With CCNE1 Amplification (NCT NCT03253679)
NCT ID: NCT03253679
Last Updated: 2023-10-17
Results Overview
ORR is defined as a complete response or partial response and consistent with Response Evaluation Criteria in Solid Tumors version 1.1 criteria. The ORR rate will be compared against a null benchmark value of 5%.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
31 participants
Primary outcome timeframe
Up to 2 years 6 months
Results posted on
2023-10-17
Participant Flow
Participant milestones
| Measure |
Treatment (Adavosertib)
Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Overall Study
STARTED
|
31
|
|
Overall Study
COMPLETED
|
30
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Treatment (Adavosertib)
Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Overall Study
Screen Failure
|
1
|
Baseline Characteristics
One participant did not receive any study agent. Thus, 30 patients were considered evaluable
Baseline characteristics by cohort
| Measure |
Treatment (Adavosertib)
n=30 Participants
Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Age, Continuous
|
65 Years
n=99 Participants • One participant did not receive any study agent. Thus, 30 patients were considered evaluable
|
|
Sex: Female, Male
Female
|
26 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=99 Participants • One participant did not receive any study agent. Thus, 30 patients were considered evaluable.
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
26 Participants
n=99 Participants • One participant did not receive any study agent. Thus, 30 patients were considered evaluable.
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants • One participant did not receive any study agent. Thus, 30 patients were considered evaluable.
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants • One participant did not receive any study agent. Thus, 30 patients were considered evaluable
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=99 Participants • One participant did not receive any study agent. Thus, 30 patients were considered evaluable
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants • One participant did not receive any study agent. Thus, 30 patients were considered evaluable
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=99 Participants • One participant did not receive any study agent. Thus, 30 patients were considered evaluable
|
|
Race (NIH/OMB)
White
|
25 Participants
n=99 Participants • One participant did not receive any study agent. Thus, 30 patients were considered evaluable
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants • One participant did not receive any study agent. Thus, 30 patients were considered evaluable
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants • One participant did not receive any study agent. Thus, 30 patients were considered evaluable
|
|
Region of Enrollment
United States
|
30 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Up to 2 years 6 monthsORR is defined as a complete response or partial response and consistent with Response Evaluation Criteria in Solid Tumors version 1.1 criteria. The ORR rate will be compared against a null benchmark value of 5%.
Outcome measures
| Measure |
Treatment (Adavosertib)
n=30 Participants
Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Objective Response Rate (ORR)
|
27 percentage
Interval 12.0 to 46.0
|
SECONDARY outcome
Timeframe: Up to 2 years 6 monthsEstimated using the Kaplan-Meier Method.
Outcome measures
| Measure |
Treatment (Adavosertib)
n=30 Participants
Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
To Evaluate the Proportion of Patients Alive and Progression Free of Treatment With AZD1775 in Patients With Advanced Refractory Cancers With CCNE1 Amplification.
|
37 percentage
Interval 20.0 to 56.0
|
SECONDARY outcome
Timeframe: Up to 2 years 6 monthsEstimated using the Kaplan-Meier Method.
Outcome measures
| Measure |
Treatment (Adavosertib)
n=30 Participants
Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
To Evaluate Time Until Death or Disease Progression.
|
9.9 Months
Interval 4.8 to 15.0
|
SECONDARY outcome
Timeframe: Up to 2 years 6 months(time to progression on AZD1775/ time to progression on last line of therapy \>= 1.3).
Outcome measures
| Measure |
Treatment (Adavosertib)
n=30 Participants
Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Duration of Responses
|
4.1 Months
Interval 1.8 to 6.4
|
SECONDARY outcome
Timeframe: Up to 2 years 6 monthsImmunohistochemistry, reverse phase protein arrays, and next generation sequencing for targeted exome panel are used to reveal potential biomarkers predicting major clinical outcomes, and potential mechanisms of acquired resistance by comparing molecular signatures at baseline versus at time of relapse in responders.
Outcome measures
| Measure |
Treatment (Adavosertib)
n=30 Participants
Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Identify Potential Predictive Biomarkers Beyond the Genomic Alteration by Which Treatment is Assigned or Resistance Mechanisms Using Additional Genomic, RNA, Protein and Imaging-based Assessment Platforms.
TP53 gene aberration
|
27 Participants
|
|
Identify Potential Predictive Biomarkers Beyond the Genomic Alteration by Which Treatment is Assigned or Resistance Mechanisms Using Additional Genomic, RNA, Protein and Imaging-based Assessment Platforms.
AKT2 amplification
|
7 Participants
|
|
Identify Potential Predictive Biomarkers Beyond the Genomic Alteration by Which Treatment is Assigned or Resistance Mechanisms Using Additional Genomic, RNA, Protein and Imaging-based Assessment Platforms.
MYC amplification
|
5 Participants
|
|
Identify Potential Predictive Biomarkers Beyond the Genomic Alteration by Which Treatment is Assigned or Resistance Mechanisms Using Additional Genomic, RNA, Protein and Imaging-based Assessment Platforms.
CCND2 amplification
|
3 Participants
|
|
Identify Potential Predictive Biomarkers Beyond the Genomic Alteration by Which Treatment is Assigned or Resistance Mechanisms Using Additional Genomic, RNA, Protein and Imaging-based Assessment Platforms.
NOTCH1 mutation
|
3 Participants
|
Adverse Events
Treatment (Adavosertib)
Serious events: 20 serious events
Other events: 30 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Treatment (Adavosertib)
n=30 participants at risk
Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Metabolism and nutrition disorders
Dehydration
|
13.3%
4/30 • Up to 2 years 6 months
|
|
Gastrointestinal disorders
Abdominal pain
|
6.7%
2/30 • Up to 2 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.7%
2/30 • Up to 2 years 6 months
|
|
General disorders
Fatigue
|
6.7%
2/30 • Up to 2 years 6 months
|
|
Vascular disorders
Thromboemolic event
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Gastrointestinal disorders
Diarrhea
|
6.7%
2/30 • Up to 2 years 6 months
|
|
Gastrointestinal disorders
Vomiting
|
6.7%
2/30 • Up to 2 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.3%
1/30 • Up to 2 years 6 months
|
|
General disorders
Fever
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Gastrointestinal disorders
Nausea
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Renal and urinary disorders
Acute kidney failure
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Infections and infestations
Sepsis
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Nervous system disorders
Delirium
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Vascular disorders
Portal vein thrombosis
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Nervous system disorders
Depression
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
3.3%
1/30 • Up to 2 years 6 months
|
|
General disorders
Non-hemolytic transfusion reaction
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Infections and infestations
Bladder infection
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Renal and urinary disorders
Renal failure
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Renal and urinary disorders
Urinary tract obstruction
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Infections and infestations
Skin infection
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Investigations
Blood bilirubin increased
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Nervous system disorders
Confusion
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Injury, poisoning and procedural complications
Fall
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Investigations
Creatinine increased
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
3.3%
1/30 • Up to 2 years 6 months
|
|
General disorders
Disease progression
|
3.3%
1/30 • Up to 2 years 6 months
|
|
Infections and infestations
Enterocolitis infections
|
3.3%
1/30 • Up to 2 years 6 months
|
Other adverse events
| Measure |
Treatment (Adavosertib)
n=30 participants at risk
Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
53.3%
16/30 • Up to 2 years 6 months
|
|
Investigations
ALP increased
|
30.0%
9/30 • Up to 2 years 6 months
|
|
Investigations
ALT increased
|
23.3%
7/30 • Up to 2 years 6 months
|
|
Blood and lymphatic system disorders
Anemia
|
86.7%
26/30 • Up to 2 years 6 months
|
|
Metabolism and nutrition disorders
Anorexia
|
30.0%
9/30 • Up to 2 years 6 months
|
|
Investigations
AST increased
|
23.3%
7/30 • Up to 2 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
36.7%
11/30 • Up to 2 years 6 months
|
|
Gastrointestinal disorders
Constipation
|
40.0%
12/30 • Up to 2 years 6 months
|
|
Investigations
Creatinine increased
|
16.7%
5/30 • Up to 2 years 6 months
|
|
Metabolism and nutrition disorders
Dehydration
|
13.3%
4/30 • Up to 2 years 6 months
|
|
Gastrointestinal disorders
Diarrhea
|
93.3%
28/30 • Up to 2 years 6 months
|
|
Nervous system disorders
Dizziness
|
26.7%
8/30 • Up to 2 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
30.0%
9/30 • Up to 2 years 6 months
|
|
General disorders
Edema limbs
|
50.0%
15/30 • Up to 2 years 6 months
|
|
General disorders
Fatigue
|
66.7%
20/30 • Up to 2 years 6 months
|
|
Nervous system disorders
Headache
|
23.3%
7/30 • Up to 2 years 6 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
16.7%
5/30 • Up to 2 years 6 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
66.7%
20/30 • Up to 2 years 6 months
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
33.3%
10/30 • Up to 2 years 6 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
46.7%
14/30 • Up to 2 years 6 months
|
|
Investigations
Lymphocyte count decreased
|
40.0%
12/30 • Up to 2 years 6 months
|
|
Gastrointestinal disorders
Nausea
|
83.3%
25/30 • Up to 2 years 6 months
|
|
Investigations
Neutrophil count decreased
|
33.3%
10/30 • Up to 2 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
20.0%
6/30 • Up to 2 years 6 months
|
|
Investigations
Platelet count decreased
|
83.3%
25/30 • Up to 2 years 6 months
|
|
Gastrointestinal disorders
Vomiting
|
40.0%
12/30 • Up to 2 years 6 months
|
|
Investigations
WBC decreased
|
40.0%
12/30 • Up to 2 years 6 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60