Overview

Condition carcinoma, squamous cell of head and neck
Treatments azd1775, cisplatin, intensity modulated radiotherapy treatments
Phase phase 1
Target WEE1
Sponsor UNC Lineberger Comprehensive Cancer Center
Collaborator AstraZeneca
Start date February 2016
End date November 2020
Trial size 24 participants
Trial identifier NCT02585973, LCCC 1430

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).

Recruiting in the following locations…

United States North Carolina and North Dakota
Other countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Other)
AZD1775 when added to standard of care concomitant chemotherapy (cisplatin) and radiation
azd1775 MK-1775 hemihydrate
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.
cisplatin cisplatin injection
40 mg/m2 IV infused over 1 hour D1 of each week of radiation
intensity modulated radiotherapy treatments IMRT
Total dose will be 70 Gy at 2Gy/fx, 35 fractions, M to Fri, for 7 weeks

Primary Outcomes

Measure
Maximum tolerated dose
time frame: 7 weeks

Secondary Outcomes

Measure
Toxicity profile (Number of patients with adverse events)
time frame: 7 weeks
Objective Response Rate
time frame: 12 weeks

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria

  • HPV/p16 (+) disease, a significant tobacco smoking history (>10 pack years) and N2b-N3 disease OR
  • HPV (-) disease, ≤ 10 years of smoking and large tumors (T2-T3) Oropharynx High risk patients include those who are either:
  • HPV (-) with >10 years of smoking, OR
  • HPV (-), ≤ 10 years of smoking and T4 disease Oral Cavity, Larynx, Hypopharynx are considered high/intermediate risk (regardless of HPV, p16 or smoking status) 4.1.5 Required initial laboratory values:
  • HgB ≥ 9.0 g/dL
  • ANC≥1500/mm3
  • Platelet count ≥ 100,000/mm3
  • Serum creatinine ≤1.5 mg/dL and/or calculated creatinine clearance ≥50 mL/min(via Cockroft and Gault, see section 12.2, Appendix B)
  • Bilirubin ≤ 1.25 x upper limits of normal (ULN)
  • AST and ALT ≤ 2.0 x ULN 4.1.6 No prior definitive surgery for HNSCC 4.1.7 Recommendation to undergo concurrent CRT, as determined by the treating physician, with a curative goal 4.1.8 Women of childbearing potential (WOCBP) should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study. WOCBP are those who have not been surgically sterilized or have not been free from menses for > 1 year. The two birth control methods can be composed of: two barrier methods or a barrier method plus a hormonal method to prevent pregnancy. Subjects should start using birth control from the screening visit and continue throughout study mandated treatment and for 90 days after the final dose of study drug. The following are considered adequate barrier methods of contraception: diaphragm, condom (by the partner), copper intrauterine device, sponge, or spermicide. Appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular agents). 4.1.9 Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy and continuing through the last dose of study therapy and for 90 days after the final dose of study drug 4.1.10 Women of childbearing potential (WOCBP) must have negative pregnancy test within 72 hours prior to D1 of treatment 4.1.11 Ability to swallow oral medications 4.1.12 As determined by the enrolling physician or protocol designee, ability of the patient to understand and comply with study procedures for the entire length of the study 4.1.13 Informed consent reviewed and signed

Exclusion Criteria

    Additional Information

    Official title 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)
    Principal investigator Bhishamjit Chera, MD
    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.
    Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
    Information provided to ClinicalTrials.gov by UNC Lineberger Comprehensive Cancer Center.
    Location data was received from the National Cancer Institute and was last updated in February 2017.