Cancers use 'defence mechanisms' to hide from the immune system and teach the immune system
not to destroy cancer cells. AMG 319 works by blocking these defence mechanisms in the
tumour. It targets and blocks an important protein called PI3K delta.
In the laboratory this leads to removal of a group of inhibitory immune cells. Releasing the
immune brakes leads to immune attack and destruction of cancer cells.
AMG 319 looks promising in laboratory studies and in a very early study in a small number of
patients with leukaemia and CRUK now wish to find out if it will be useful in treating
patients with head and neck cancer.
This study is a randomised, doubleblind, placebo controlled Phase II trial looking at the
effects of giving AMG 319 to patients with the type of head and neck cancer squamous cell
carcinoma (HNSCC) with the worst outcomes. These are the cancers that are not caused by
human papilloma virus (HPV). CRUK proposes to treat patients prior to resection surgery so
that investigators can study the effect of AMG 319 on the cancer in fine detail.
Approximately 54 patients with HPV negative HNSCC of the hypopharynx, oropharynx or oral
cavity will be entered into the study. Patients will be randomly assigned to one of two
treatment groups and will receive between 21 and 30 days of oral dosing with AMG 319 or
placebo immediately before resection surgery.
1. Histologically proven HNSCC of the hypopharynx, oropharynx or oral cavity (T1-T4,
N0-N3) 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.
HPV negativity will be determined initially on clinical grounds (morphology and location)
and formally confirmed by demonstrating negative p16 staining by immunohistochemistry.
Formal confirmation must be sought prior to trial entry, but if results are unavailable
the patient may still be enrolled.
Patients presenting with recurrence or a secondary primary HNSCC 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.
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 2.0 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
1. Prior radiotherapy, immunotherapy, chemotherapy or other anti-cancer therapy (excluding
surgery) for HNSCC.
2. Current malignancies of other types with the exception of adequately treated
cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma
of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior
malignancy, have no evidence of that disease for five years or more or are deemed at
negligible risk for recurrence, are eligible for the trial. Patients must not have
received radiotherapy, immunotherapy, chemotherapy or other anti-cancer therapy within 5
years prior to trial entry.
3. Female patients who are able to become pregnant (or already pregnant or lactating).
However, those patients who have a negative serum or urine pregnancy test before enrolment
and agree to use two highly effective forms of contraception (oral; injected or implanted
hormonal contraception and condom; have an intra-uterine device and condom; diaphragm with
spermicidal gel and condom) effective at the first administration of AMG 319, throughout
the trial and for 6 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 one form of highly effective contraception
[condom plus spermicide] effective at the first administration of AMG 319, throughout the
trial and for 6 months afterwards). Men with pregnant or lactating partners must be
advised to use barrier method contraception (for example: condom plus spermicidal gel) to
prevent exposure to 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
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. Active or chronic hepatitis B or hepatitis C infection. If there is clinical suspicion
of infection this must be ruled out by appropriate serological and PCR testing.
11. Serologically positive for human immunodeficiency virus (HIV).
12. QTc >470 msec (Friderica [QTc F] correction) or a history or family history of QT
13. Treatment with medications known to cause QTc interval prolongation within seven days
prior to receiving the first dose of AMG 319 or placebo.
14. 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.
15. Any other condition which in the Investigator's opinion would not make the patient a
good candidate for the clinical trial.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both