NCT02585973

Dose-escalating AZD1775 + Concurrent Radiation + Cisplatin for Intermediate/High Risk HNSCC

Phase Ib Trial of Dose-escalating AZD1775 in Combination With Concurrent Radiation and Cisplatin for Intermediate and High Risk Head and Neck Squamous Cell Carcinoma (HNSCC)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: UNC Lineberger Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This open label, single-arm, Phase 1b study is designed to identify the maximum tolerated dose (MTD) using a traditional 3+3 dose escalation design of the WEE-1 inhibitor AZD1775 when added to standard of care chemotherapy (cisplatin) and radiation for the treatment of locally advanced squamous cell cancer of the head and neck (HNSCC).

Detailed description

This open label, single-arm, Phase 1b study is designed to identify the maximum tolerated dose (MTD) using a traditional 3+3 dose escalation design of the WEE-1 inhibitor AZD1775 when added to standard of care chemotherapy (cisplatin) and radiation for the treatment of locally advanced squamous cell cancer of the head and neck (HNSCC). The first cohort will include a starting dose of 50 mg AZD1775 given twice daily (BID) for three consecutive days (M-W) concomitantly with standard of care cisplatin and radiation. AZD1775 doses will be escalated in 50 mg increments up to 200 mg BID (M-W) in subsequent cohorts to determine the MTD. Up to 24 patients will be enrolled, depending on the rate of dose limiting toxicity (DLT). The investigators plan to characterize the toxicity (and safety) profile of this regimen. Secondary objectives include determination of the recommended phase 2 dose (RP2D; based on safety and other data considerations), objective response rate (ORR) at 12 weeks and progression free survival (PFS). the investigators will also estimate overall survival (OS) if the effective sample size allows. The investigators hypothesize that the investigators' proposed regimen is safe, and will yield an improved ORR and PFS over historical controls. Correlative studies will be performed on archival tissue, and on optional fresh biopsies performed at baseline and mid-treatment. The investigators will explore associations between p53 mutational status at baseline as well as changes in checkpoint markers, with ORR, PFS and OS. Finally, the investigators plan to describe possible changes in QOL, speech and swallowing.

Conditions

• Carcinoma, Squamous Cell of Head and Neck

Interventions

Type	Name	Description
DRUG	AZD1775	AZD1775 given twice daily (BID) for three consecutive days (M-W) concomitantly with standard of care cisplatin and radiation. AZD1775 doses will be escalated in 50 mg increments up to 200 mg BID (M-W) in subsequent cohorts to determine the MTD.
DRUG	Cisplatin	40 mg/m2 IV infused over 1 hour D1 of each week of radiation
RADIATION	Intensity Modulated Radiotherapy Treatments	Total dose will be 70 Gy at 2Gy/fx, 35 fractions, M to Fri, for 7 weeks

Timeline

• Start date: 2015-10-26
• Primary completion: 2019-06-14
• Completion: 2021-06-23
• First posted: 2015-10-26
• Last updated: 2021-06-29

Locations

1 site across 1 country: United States