human papillomavirus (HPV) positive and negative head and neck squamous cell carcinoma (HNSCC) MedDRA version: 20.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: AMG 319
Product Code: AMG 319
Pharmaceutical Form: Capsule
INN or Proposed INN: AMG 319
Current Sponsor code: AMG 319 hydr
Sponsors
Cancer Research UK
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Histologically proven HNSCC of the hypopharynx, oropharynx, oral cavity ,supraglottis or larynx (except T1 glottic tumours) for whom surgery with curative intent ± post-operative radiotherapy or chemoradiotherapy is considered the primary treatment of choice. Surgery should be scheduled to take place no sooner than 21 days and no later than 30 days post first dose of AMG 319 or placebo. Patients presenting with recurrence can be considered for inclusion, as long as their previous treatment did not include radiotherapy ± chemotherapy or any other anti-cancer therapy i.e. treated with surgery alone and this did not take place within 6 months prior to trial entry. Patients presenting with a second primary HNSCC can be considered for inclusion, as long as any previous radiotherapy, chemotherapy or any other anti-cancer therapy was completed more than 5 years prior to trial entry. 2) Patients considered fit to undergo curative resection surgery. 3) Haematological and biochemical indices within the ranges shown below. These measurements must be performed within eight days prior to the patient receiving the first dose of AMG 319 or placebo. Laboratory Test Value required •Haemoglobin (Hb) = 100 g/L •Absolute neutrophil count = 1.5 x 10^9/L •Platelet count = 100 x 10^9/L •Bilirubin = 1.5 x upper limit of normal ULN •Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) = 2.5 x ULN •Alkaline Phosphatase (alk phos/ALP) = 2.5 x ULN •Amylase = 2 x ULN •Calculated creatinine clearance (using the Wright or Cockcroft-Gault formula) = 50 mL/min 4) 18 years or over at the time informed consent is given. 5) Written (signed and dated) informed consent and capable of co-operating with treatment and follow-up. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 42 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: 1) Prior radiotherapy, immunotherapy, chemotherapy or other anti-cancer therapy (excluding surgery) for current HNSCC. 2) Patients should be excluded from the trial if they have active or previous malignancies of other types which in the investigator's opinion would mean they are not a good candidate for the clinical trial. 3) Female patients who are able to become pregnant (or are already pregnant or lactating). However, those patients who have a negative serum or urine pregnancy test before enrolment and agree to use two forms of contraception (one effective form plus a barrier method) [oral, injected or implanted hormonal contraception and condom; intra-uterine device and condom; diaphragm with spermicidal gel and condom] or agree to sexual abstinence*, effective from the first administration of AMG 319 throughout the trial and for six months afterwards are considered eligible. 4) Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using a barrier method of contraception [condom plus spermicide] or to sexual abstinence* effective from the first administration of AMG 319, throughout the trial and for six months afterwards. Men with partners of child-bearing potential must also be willing to ensure that their partner uses an effective method of contraception for the same duration for example, hormonal contraception, intrauterine device, diaphragm with spermicidal gel or sexual abstinence). Men with pregnant or lactating partners must be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure of the foetus or neonate. 5) Patients unable to swallow oral medications (trial medication must not be chewed, crushed, dissolved or divided). 6) Major thoracic or abdominal surgery from which the patient has not yet recovered. 7) At high medical risk because of non-malignant systemic disease including active uncontrolled infection. 8) Active or uncontrolled auto-immune disease which may require systemic immunomodulator therapy during the trial treatment period. Exceptions to this are atopic dermatitis and psoriasis not requiring systemic treatment. 9) Long term use of systemic corticosteroids with the exception of replacement treatment. Discontinuation of steroid use within seven days prior to receiving the first dose of AMG 319 or placebo would be acceptable. Inhaled and topical steroids are permitted. 10) Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV). If there is clinical suspicion of infection this must be ruled out by appropriate serological and PCR testing. 11) QTc > 470 msec (Friderica [QTc F] correction) or a history or family history of QT prolongation. 12) Regular and/or prolonged treatment with medications known to cause QTc interval prolongation within seven days prior to receiving the first dose of AMG 319 or placebo. 13) Is a participant or plans to participate in another interventional clinical trial, whilst taking part in this Phase IIa trial of AMG 319. Participation in an observational trial or interventional clinical trial which does not involve administration of an IMP would be acceptable 14) Any other cond
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess changes in immune infiltration in tumour before and after treatment with AMG 319. To assess the safety and toxicity profile of AMG 319 in HNSCC. ; Secondary Objective: To investigate the pharmacokinetic behaviour of AMG 319. To document possible tumour response to neoadjuvant AMG 319. ; Primary end point(s): • Detection of a greater than 2-fold increase in CD8+ effector T cell numbers in tumour tissue after treatment with AMG 319 as assessed by immunohistochemistry. • Determining causality of each adverse event to AMG 319 and grading severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.02. ; Timepoint(s) of evaluation of this end point: • CD8+ effector T cell numbers in tumour tissue: Pre and post treatment biopsies • Determining causality of each adverse event to AMG 319: continually reviewed | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Determining the steady state concentration of AMG 319 in blood. • Re-assessment of tumour size immediately prior to resection surgery with Magnetic Resonance Imaging (MRI) or Computerised Tomography (CT) using Immune-Related Response Criteria (irRC). ; Timepoint(s) of evaluation of this end point: • Concentration of AMG 319 in blood: Blood samples for PK analysis to be collected pre-dose on Day 8 (± 1 day), Day 15 (± 1 day) and Day 22 • Re-assessment of tumour size immediately prior to resection surgery (- 3 days) | — |
Countries
United Kingdom
Contacts
Public ContactCentre for Drug Development
Cancer Research UK
Outcome results
None listed