Window of opportunity trial of Tarloxotinib combined with stereotactic body radiotherapy (SBRT) in advanced human papilloma virus (HPV) negative head & neck cancer.

Phase 1

• Conditions: head and neck cancer; Cancer - Head and neck

• Registration Number: ACTRN12622000369729
• Lead Sponsor: Te Puriri O Te Ora Directorate of Cancer & Blood at Auckland City Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-03-02
• Study Completion: 2023-10-12
• Last Update Posted: 23 October 2023

Recruitment & Eligibility

• Status: Stopped early
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

Stage III or stage IV advanced p16-ve HNSCC oral cavity, oropharynx, larynx or hypopharynx planned for definitive surgical resection.
1. Aged 18 years or older
2. Histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx planned for definitive surgical resection.
3. Stage III or stage IV.
4. Primary able to be visualised on CT.
5. No prior treatment for head and neck cancer
6. Adequate haematological, renal, and hepatic function as defined by,
a.Absolute neutrophil count (ANC, segs + bands) greater than or equal to 1.5 x 109/L
b.Platelet count greater than or equal to 100 x 109/L
c.Haemoglobin greater than or equal to 90 g/L
d.Total bilirubin greater than or equal to 1.5 x upper normal limit
e.ALT greater than or equal to 2.5 x upper normal limit
f.Calculated creatinine clearance (Cockcroft-Gault formula) or isotopic GFR less than 55ml/min
1.ECOG performance status score of 0-1
2.Patients with inactive/asymptomatic carrier, chronic, or active hepatitis B virus (HBV) must have HBV DNA less than 500 IU/mL (or 2500 copies/mL) at Screening
3.Adequate cardiac function meeting all of the following ECG criteria:
a.No evidence of second or third degree atrioventricular block
b.No clinically significant arrhythmia (i.e., pauses of more than 4 seconds, ventricular tachycardia of any duration, supraventricular tachycardia more than 4 beats/minute)
c. QRS interval less than or equal to 110 msec
d. QTc interval of less than 450 msec as calculated according to Fridericia’s formula (QTcF = QT/[R to R interval]0.33)
e. PR interval less than or equal to 200 msec (does not apply to people with chronic stable atrial fibrillation or atrial flutter as determined by the Investigator)
4.Participants capable of childbearing are using adequate contraception and intend to continue use of contraception for at least 6 months following completion of treatment
5.Negative pregnancy test within 72 hours prior to randomisation of women who are of childbearing potential
6.Suitable for follow-up for at least 24 months as per trial protocol.
7.Sufficient proficiency in English, cognitive capacity and willingness to complete questionnaires

Exclusion Criteria

History of unknown primary of the head and neck.
2. Women who are pregnant or lactating.
3. Previous radiotherapy to the area to be treated (excluding superficial radiotherapy for a cutaneous malignancy)
4. Prior EGFR targeted therapy of any kind
5. History of myocardial infarction within 12 months prior to study entry, uncontrolled congestive heart failure, unstable angina, active cardiomyopathy, unstable arrhythmia, clinically significant thrombotic or embolic events within 3 months prior to enrollment (diagnosis of deep vein thrombosis allowed), uncontrolled psychotic disorders, active serious infections, active peptic ulcer disease, immunosuppression due to post-organ transplantation or use of immunosuppressants for autoimmune disorders.
6.Clinically active or symptomatic interstitial lung disease (ILD) or interstitial pneumonitis.
7.Any active malignancy less than or equal to 2 years before the first dose of study drug(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast)
8. A known history hepatitis C virus (HCV) infection, except for patients with cured HCV.
9. Known human HIV infection
10.Uncontrolled diabetes or > Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management, or greater than or equal to Grade 3 hypoalbuminemia occurring less than or equal to 14 days before first dose of study drug
11. Administered a live vaccine less than or equal to 4 weeks before first dose of study drug Note: Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines, and are not allowed
12. Underlying medical conditions (including laboratory abnormalities) or alcohol or drug abuse or dependence that will be unfavorable for the administration of study drug or that will affect the explanation of drug toxicity or AEs or result in insufficient or might impair compliance with study conduct.
13. Receiving medications that carry a risk of QTc prolongation and Torsade de Pointes (see concomitant medications section). Enrollment is allowed if discontinuation of such medications occurs at least 5 half-lives before Cycle 1 Day 1 Tarloxotinib.
14.Personal or familial history of Long QT Syndrome, sudden death, or Torsade de Pointes

15.History of severe allergic or anaphylactic reactions or hypersensitivity to compounds of similar chemical or biologic composition as tarloxotinib

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The incidence of treatment related serious adverse events associated with Tarloxotinib and SBRT study protocol resulting in delay to surgery beyond day 39. Adverse events will be assessed using Common Toxicity Criteria for Adverse Events (CTCAE v5). Examples od adverse events which could be relevant include diarrhoea and macula-papular rash.[ day 39 of study protocol.]