AZD1775 in Treating Patients With Advanced Refractory Solid Tumors With CCNE1 Amplification
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03253679|
Recruitment Status : Suspended (Other - Protocol amendment required for expansion)
First Posted : August 18, 2017
Last Update Posted : April 20, 2021
|Condition or disease||Intervention/treatment||Phase|
|Advanced Malignant Solid Neoplasm Refractory Malignant Solid Neoplasm||Drug: Adavosertib||Phase 2|
I. To evaluate the proportion of patients with the objective response rate (ORR) to adavosertib (AZD1775) in patients with advanced refractory cancers with CCNE1 amplification.
I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with AZD1775 in patients with advanced refractory cancers with CCNE1 amplification.
II. To evaluate proportion of patients with extended time to progression (time to progression on AZD1775/ time to progression on last line of therapy >= 1.3).
III. To evaluate time until death or disease progression. IV. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.
Patients receive adavosertib orally (PO) once daily (QD) on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of AZD1775, a Wee1 Inhibitor, in Patients With CCNE1 Amplification|
|Actual Study Start Date :||September 24, 2018|
|Estimated Primary Completion Date :||September 30, 2021|
|Estimated Study Completion Date :||September 30, 2021|
Experimental: Treatment (adavosertib)
Patients 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) [ Time Frame: Up to 6 months ]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%.
- Incidence of adverse events and serious adverse events [ Time Frame: Up to 2 years ]Will be assessed according to the National Cancer (NCI) Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Will assess clinical symptoms and laboratory values, evaluate vital signs and perform physical exams, with a special attention to treatment-related fatigue, gastrointestinal symptoms, cardiovascular events, myelosuppression, and neurotoxicity.
- Incidence grade >= 2 adverse events adverse [ Time Frame: Up to 2 years ]According to the NCI CTCAE version 4.0.
- Deaths [ Time Frame: Up to 2 years ]Deaths during the study will be documented.
- Withdrawals [ Time Frame: Up to 2 years ]Withdrawals from the study due to treatment-related adverse events will be documented.
- Change in treatment regimen [ Time Frame: Up to 2 years ]Change of the treatment regimen such as dose delay and dose reduction over time by dose level due to treatment-related adverse events will be documented. Differences in categorical variables will be assessed using the Fisher exact test.
- Progression free survival (PFS) [ Time Frame: Up to 2 years ]Estimated using the Kaplan-Meier Method.
- Overall survival (OS) [ Time Frame: Up to 2 years ]Estimated using the Kaplan-Meier Method.
- Molecular profiling [ Time Frame: Baseline ]Fisher exact test is used to associate the baseline molecular profiling, with ORR. Log rank test is used to associate the baseline molecular profiling, with estimated PFS and OS.
- Potential biomarkers predicting major clinical outcomes and potential mechanisms of acquired resistance [ Time Frame: Up to 2 years ]Immunohistochemistry, 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03253679
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010|
|United States, Colorado|
|University of Colorado Hospital|
|Aurora, Colorado, United States, 80045|
|United States, District of Columbia|
|MedStar Georgetown University Hospital|
|Washington, District of Columbia, United States, 20007|
|United States, Florida|
|University of Florida Health Science Center - Gainesville|
|Gainesville, Florida, United States, 32610|
|United States, Kentucky|
|University of Kentucky/Markey Cancer Center|
|Lexington, Kentucky, United States, 40536|
|United States, New York|
|NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center|
|New York, New York, United States, 10032|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|United States, Pennsylvania|
|University of Pittsburgh Cancer Institute (UPCI)|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Siqing Fu||University of Texas MD Anderson Cancer Center LAO|