WEE1 Inhibitor MK-1775, Docetaxel, and Cisplatin Before Surgery in Treating Patients With Borderline Resectable Stage III-IVB Squamous Cell Carcinoma of the Head and Neck
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|ClinicalTrials.gov Identifier: NCT02508246|
Recruitment Status : Completed
First Posted : July 24, 2015
Last Update Posted : March 13, 2019
|Condition or disease||Intervention/treatment||Phase|
|Head and Neck Squamous Cell Carcinoma||Drug: Cisplatin Drug: Docetaxel Other: Laboratory Biomarker Analysis Other: Pharmacological Study Procedure: Therapeutic Conventional Surgery Drug: WEE1 Inhibitor AZD1775||Phase 1|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Clinical Trial of AZD1775 in Combination With Neoadjuvant Weekly Docetaxel and Cisplatin Prior to Surgery in Squamous Cell Carcinoma of the Head and Neck (HNSCC)|
|Actual Study Start Date :||July 22, 2015|
|Actual Primary Completion Date :||April 26, 2018|
|Actual Study Completion Date :||April 26, 2018|
Experimental: Treatment (WEE1 inhibitor MK-1, cisplatin, docetaxel, surgery)
Patients receive WEE1 inhibitor MK-1775 PO BID on days 2-4, 9-11, and 16-18, and day -7 prior to course 1, day 1 for PD assessment. Patients also receive cisplatin IV on days 1 (or up to two days after last dose of WEE1 inhibitor MK-1775 lead-in is completed), 8 (or 7 days after first chemotherapy dose), and 15, and docetaxel IV on days 1, 8, and 15. Patients experiencing progressive disease undergo surgical resection. Patients not deemed surgically resectable proceed to chemoradiation as clinically indicated. Patients experiencing stable disease or partial response may receive 2 additional courses of treatment every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Procedure: Therapeutic Conventional Surgery
Drug: WEE1 Inhibitor AZD1775
- Incidence of adverse events graded according to the NCI CTCAE version 4.03 [ Time Frame: Up to 2 years post-treatment ]Summary tables and graphic displays, as appropriate, will be prepared to examine the distribution of these toxicities per cycle.
- MTD of AZD1775, based on the incidence of dose limiting toxicity (DLT), graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 [ Time Frame: 28 days ]DLT is defined as any adverse event judged by the investigator to be drug-related (i.e., causality rated as possible or greater) that is assessed as grade 3 or worse. Summary tables and graphic displays, as appropriate, will be prepared to examine the distribution of these toxicities per cycle.
- Objective response (complete response, partial response, stable disease or progressive disease) according to Response Evaluation Criteria In Solid Tumors [ Time Frame: Up to 5 years post-treatment ]
- Pharmacodynamic profile of AZD1775 [ Time Frame: Time of surgery or up to day 29 ]Pharmacodynamic parameters will be studied during lead-in monotherapy to determine target engagement, mainly phosphorylated WEE1 and CDC2. Prior to treatment normal tissue in the opposite side of the tumor in the oral mucosa will be used for controls. Biological specificity will be verified by assessing the phosphorylated state of WEE1 and downstream effector molecules: total CDC2, ptyr15 CDC2, for G2/M. Other relevant biomarkers and molecular or genetic analyses may be performed.
- PK profile of WEE1 inhibitor MK-1775 with docetaxel and cisplatin [ Time Frame: Pre-dose and at 1, 2, 4, 6, and 8-10 hours on days 2 and 4 of course 1, and pre-dose on day 3 of course 1 ]Maximum concentration and mean terminal half-life will be focused on during PK analysis.
- Progression-free survival (PFS) duration [ Time Frame: Up to 5 years post-treatment ]PFS will be determined in days or weeks and waterfall plots and graphical data will be provided where suitable.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02508246
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Eduardo Mendez||Fred Hutch/University of Washington Cancer Consortium|