Human Papillomavirus (HPV)Phase 2NCT02540928

AMG 319 in HPV Positive and Negative HNSCC

A Phase 2 study testing AMG 319 hydrate in people with Human Papillomavirus (HPV) and Positive or Negative Head and Neck Squamous Cell Carcinoma (HNSCC) of the Hypopharynx, Oropharynx, Oral Cavity, Supraglottis or Larynx, run by Cancer Research UK at 5 sites in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

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 Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Human Papillomavirus (HPV), Positive or Negative Head and Neck Squamous Cell Carcinoma (HNSCC) of the Hypopharynx, Oropharynx, Oral Cavity, Supraglottis or Larynx
What is being tested?: AMG 319 hydrate
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 35 participants
Where: 5 sitesUnited Kingdom
Study dates: Oct 2015to 3 May 2018
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.
Patients considered fit to undergo curative resection surgery.
Haematological and biochemical indices within the ranges shown below:
Laboratory Test Value required

Show all 15Show fewer

Haemoglobin (Hb) ≥100 g/L
Absolute neutrophil count ≥1.5 x 109/L
Platelet count ≥100 x 109/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
18 years or over at the time informed consent is given.
Written (signed and dated) informed consent and capable of co-operating with treatment and follow up.

Who cannot join

Prior radiotherapy, immunotherapy, chemotherapy or other anti-cancer therapy (excluding surgery) for current HNSCC.
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.
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.
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.
Patients unable to swallow oral medications (trial medication must not be chewed, crushed, dissolved or divided).
Major thoracic or abdominal surgery from which the patient has not yet recovered.

Show all 14Show fewer

At high medical risk because of non malignant systemic disease including active uncontrolled infection.
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.
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.
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.
QTc >470 msec (Friderica [QTc F] correction) or a history or family history of QT prolongation.
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.
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.
Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United Kingdom5 sites

Aintree University Hospital - Clatterbridge Cancer Centre
Liverpool, CH63 4JY
Churchill Hospital, Blenheim H&N Unit
Oxford, OX3 7LE
Poole Hospital
Poole, BH15 2JB
Queen Alexandra Hospital, Department of Oral and Maxillofacial Surgery
Portsmouth, PO6 3LY
Southampton General Hospital
Southampton, SO16 6YD

Other trials in United Kingdom

About this study

Official title: A Cancer Research UK Randomised, Double Blind, Placebo Controlled Phase IIa Trial of AMG 319 Given Orally as a Neoadjuvant Therapy in Patients With Human Papillomavirus (HPV) Positive and Negative Head and Neck Squamous Cell Carcinoma (HNSCC)

Read the 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 we 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 either human papilloma virus (HPV) positive or negative head and neck cancer squamous cell carcinoma (HNSCC). We propose to treat patients prior to resection surgery so that we can study the effect of AMG 319 on the cancer in fine detail.

Approximately 54 patients with HPV positive or negative HNSCC of the hypopharynx, oropharynx, oral cavity, supraglottis or larynx will be entered into the study. Patients will be randomly assigned to one of two treatment groups and will receive between 20 and 29 days of oral dosing with AMG 319 or placebo immediately before resection surgery.

Conditions: Human Papillomavirus (HPV), Positive or Negative Head and Neck Squamous Cell Carcinoma (HNSCC) of the Hypopharynx, Oropharynx, Oral Cavity, Supraglottis or Larynx
Being tested: AMG 319 hydrate, Placebo
Medical subject headings: Squamous Cell Carcinoma of Head and Neck, Laryngeal Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AMG 319 hydrateDrug
PlaceboDrug

Study groups in NCT02540928
Study group	Role	What they receive
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 20 days and a maximum of 29 days prior to resection surgery Receives: Drug: 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 20 days and a maximum of 29 days prior to resection surgery Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Changes in CD8+ effector T cell numbers in tumour tissue
Measured: Screening and Surgery
Treatment emergent adverse events
Measured: Assessed until 60 days after a patients last dose

Secondary outcomes (2)

Steady State AMG 319 concentration in blood
Measured: Days 8, 15 pre dose & Day 22
Changes in tumour size
Measured: Screening and Pre-surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 20153 May 2018

First posted4 Sep 2015 (estimated)
Study startOct 2015
Primary completion3 May 2018
Study completion3 May 2018

Why it stopped: Safety Reasons

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Human Papillomavirus (HPV)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Enrolment: 35 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02540928
Sponsor's protocol ID: CRUKD/15/004
Status last verified: Jul 2018
First submitted: 25 Aug 2015
Last updated: 18 Jul 2018
Results posted: No
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 1/2
Clinical Trial to Assess the Safety, Tolerability, Reactogenicity, and Immunogenicity of a 10 Valent Human Papillomavirus Virus (10vHPV) Vaccine
Human Papillomavirus Infection
Active, not recruitingPhase 4
Comparing Immune Response of 2 vs 3 HPV Doses (27-45 Years Old)
Immunization, HPV Infection
Not yet recruitingPhase 2
Combination Bevacizumab and PRGN-2012 in Adults With Recurrent Respiratory Papillomatosis (RRP)
Respiratory Recurrent Papillomatosis (RRP), Human Papillomavirus (HPV)
RecruitingPhase 2
A Study of the Preliminary Efficacy of DARE-HPV to Treat High-risk Persistent Human Papillomavirus (hrHPV)
Human Papilloma Virus (HPV), High-risk Human Papillomavirus Infection
RecruitingPhase 2
A Single Arm Phase II Trial in p16-positive Oropharynx Cancer of Selective Dose De-escalation of nodAl VolumEs at Minimal Risk and Primary Site Disease (SAVED)
Head and Neck Cancer, Head and Neck Squamous Cell Cancer

All Human Papillomavirus (HPV) trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Cancer Research UK Randomised, Double Blind, Placebo Controlled Phase IIa Trial of AMG 319 Given Orally as a Neoadjuvant Therapy in Patients With Human Papillomavirus (HPV) Positive and Negative Head and Neck Squamous Cell Carcinoma (HNSCC)
ClinicalTrials.gov ID: NCT02540928
Acronym / sponsor ID: CRUKD/15/004
Conditions: Human Papillomavirus (HPV), Positive or Negative Head and Neck Squamous Cell Carcinoma (HNSCC) of the Hypopharynx, Oropharynx, Oral Cavity, Supraglottis or Larynx
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Safety Reasons
Enrolment: 35 participants (actual)
Lead sponsor: Cancer Research UKUniversity, hospital or other
Study start: Oct 2015
Primary completion: 3 May 2018 (actual)
Study completion: 3 May 2018 (actual)
First posted: 4 Sep 2015 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Number of arms: 2

Arm	Type	Receives
AMG 319 Hydrate	Experimental	Drug: AMG 319 hydrateUp 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 20 days and a maximum of 29 days prior to resection surgery
Placebo	Placebo comparator	Drug: PlaceboUp to 18 patients will be randomised into the Placebo arm to receive Placebo once daily administered orally for a minimum of 20 days and a maximum of 29 days prior to resection surgery

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (15 listed)

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.
Patients considered fit to undergo curative resection surgery.
Haematological and biochemical indices within the ranges shown below:

Key exclusion criteria (14 listed)

Prior radiotherapy, immunotherapy, chemotherapy or other anti-cancer therapy (excluding surgery) for current HNSCC.
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.
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.
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.
Patients unable to swallow oral medications (trial medication must not be chewed, crushed, dissolved or divided).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AMG 319 hydrate	Drug	AMG 319 Hydrate
Placebo	Drug	Placebo

Primary outcome

Changes in CD8+ effector T cell numbers in tumour tissue
Time frame: Screening and Surgery
Treatment emergent adverse events
Time frame: Assessed until 60 days after a patients last dose

2 secondary outcomes

Steady State AMG 319 concentration in blood
Time frame: Days 8, 15 pre dose & Day 22
Changes in tumour size
Time frame: Screening and Pre-surgery

Results and safety

The study was stopped early (reason given: Safety Reasons). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2018.

Related trials for Human Papillomavirus (HPV)

Not yet recruitingPhase 1/2
Clinical Trial to Assess the Safety, Tolerability, Reactogenicity, and Immunogenicity of a 10 Valent Human Papillomavirus Virus (10vHPV) Vaccine
Human Papillomavirus Infection
Active, not recruitingPhase 4
Comparing Immune Response of 2 vs 3 HPV Doses (27-45 Years Old)
Immunization, HPV Infection
Not yet recruitingPhase 2
Combination Bevacizumab and PRGN-2012 in Adults With Recurrent Respiratory Papillomatosis (RRP)
Respiratory Recurrent Papillomatosis (RRP), Human Papillomavirus (HPV)
RecruitingPhase 2
A Study of the Preliminary Efficacy of DARE-HPV to Treat High-risk Persistent Human Papillomavirus (hrHPV)
Human Papilloma Virus (HPV), High-risk Human Papillomavirus Infection
RecruitingPhase 2
A Single Arm Phase II Trial in p16-positive Oropharynx Cancer of Selective Dose De-escalation of nodAl VolumEs at Minimal Risk and Primary Site Disease (SAVED)
Head and Neck Cancer, Head and Neck Squamous Cell Cancer

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Safety Reasons). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in CD8+ effector T cell numbers in tumour tissue (time frame: Screening and Surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02540928.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2018.