Clinical Trials /

AMG 319 in HPV Positive and Negative HNSCC

NCT02540928

Description:

The purpose of this study is to determine whether a drug called AMG 319 has an effect on a patient's own immune response to head and neck cancer squamous cell carcinoma (HNSCC). This study is specifically for patients who are having surgery to treat their HNSCC

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

AMG 319 in Human PapillomaVirus (HPV) Negative HNSCC

Title

  • Brief Title: AMG 319 in Human PapillomaVirus (HPV) Negative HNSCC
  • Official Title: A Cancer Research UK (CRUK) Randomised, Double-blind, Placebo-controlled Phase IIa Trial of AMG 319 Given Orally as a Neoadjuvant Therapy in Patients With Human Papillomavirus (HPV) Negative Head and Neck Squamous Cell Carcinoma (HNSCC)
  • Clinical Trial IDs

    NCT ID: NCT02540928

    ORG ID: CRUKD/15/004

    Trial Conditions

    Human Papillomavirus (HPV)

    Negative Head and Neck Squamous Cell Carcinoma (HNSCC) of the Hypopharynx, Oropharynx or Oral Cavity.

    Trial Interventions

    Drug Synonyms Arms
    AMG 319 hydrate AMG 319 Hydrate
    Placebo Placebo

    Trial Purpose

    The purpose of this study is to determine whether a drug called AMG 319 has an effect on a
    patient's own immune response to head and neck cancer squamous cell carcinoma (HNSCC). This
    study is specifically for patients who have HNSCC that is not caused by the human papilloma
    virus (HPV).

    Detailed Description

    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.

    Trial Arms

    Name Type Description Interventions
    AMG 319 Hydrate Experimental Up to 36 patients will be randomised into the Active Treatment arm to receive AMG 319 400 mg once daily administered orally for a minimum of 21 days and a maximum of 30 days prior to resection surgery AMG 319 hydrate
    Placebo Placebo Comparator Up to 18 patients will be randomised into the Placebo arm to receive Placebo once daily administered orally for a minimum of 21 days and a maximum of 30 days prior to resection surgery Placebo

    Eligibility Criteria

    Inclusion Criteria:

    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
    and follow-up.

    Exclusion Criteria:

    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
    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. 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
    prolongation.

    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

    Primary Outcome Measures

    Changes in CD8+ effector T cell numbers in tumour tissue

    Treatment emergent adverse events

    Secondary Outcome Measures

    Steady State AMG 319 concentration in blood

    Changes in tumour size

    Trial Keywords