Head and Neck CancerPhase 1NCT01818323
Phase I Trial: T4 Immunotherapy of Head and Neck Cancer
A Phase 1 study testing Intra-tumoral T4 immunotherapy in people with Head and Neck Cancer, run by King's College London at 1 site in United Kingdom.
Trial summary
The overall goal of this study is to investigate the safety of T4 immunotherapy when administered to treat loco-regional disease in Squamous Cell Cancer of the Head and Neck (SCCHN) that is not suitable for conventional active therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- Intra-tumoral T4 immunotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2015to Jan 2025
- Phase
- Phase 1
- 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 and/ or cytologically confirmed SCCHN.
- 18 years or older.
- Locally advanced and/ or recurrent head and neck cancer with or without metastatic disease (excluding brain metastases) for whom no standard therapy remains or is suitable.
- Regarding previous treatment, patients may have received prior systemic therapy, including platinum chemotherapy, at least one month earlier. In the presence of metastatic disease, recent short-course palliative radiotherapy to non-target site(s) is allowed.
- Those who refuse palliative treatment may be eligible for participation. However, their reasons for not opting for palliative treatment must be explored thoroughly.
- At least one loco-regional target lesion measurable by RECIST v1.1 criteria on CT or MRI scanning within four weeks of enrolment, and amenable to intra-tumoral injection.
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- Eastern Co-operative Oncology Performance Status of 0-2.
- Normal cardiac function as assessed by electrocardiography and either echocardiography (ECHO), or multi-gated acquisition (MUGA) scanning. Left ventricular ejection fraction must be > 50%. Assessment must take place within four weeks of enrolment.
- Haematology results within seven days of enrolment: neutrophils >1.5 x 109/L, platelets >100 x 109/L, haemoglobin >9g/dl, INR <1.5.
- Biochemistry results within seven days of enrolment: • serum creatinine <1.5 upper limit of normal • bilirubin <1.25 times normal; • ALT/ AST <2.5 times upper limit of normal (<5 times upper limit of normal if liver metastases present)
- Female patients must be postmenopausal (12 months of amenorrhea), surgically sterile or they must agree to use a physical method of contraception. Oral or injectable contraceptive agents cannot be the sole method of contraception. Women of childbearing potential (WOCB) who receive cyclophosphamide must adhere to these contraceptive requirements during the trial and until 3 months after the last dose of cyclophosphamide. Male patients, even if sterilized, must agree to use a barrier method of contraception. Male subjects must also commit to use a barrier method of contraception until at least 3 months after the end of study treatment.
- Written informed consent prior to registration.
- Eligible for NHS care in the UK.
Who cannot join
- The presence of or imminent occurrence of airway obstruction, unless tracheostomy in place.
- The presence of or imminent occurrence of tumour-mediated infiltration of major blood vessels.
- Positive history of HIV-1, HIV-2, HTLV-1, HTLV-2, Hepatitis B, Hepatitis C or syphilis infection.
- Prior splenectomy.
- Clinically active autoimmune disease. Sub-clinical or quiescent autoimmune disease does not exclude from participation.
- Treatment in the preceding week with systemic corticosteroids (> 20mg prednisolone/ day), any systemic immunomodulatory agent, radiotherapy, chemotherapy or investigational medicinal product.
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- Concurrent use of anticoagulant therapy is not permissible.
- The presence of major co-morbidity likely to impair ability to undergo trial therapy, such as recent myocardial infarction, congestive cardiac failure or uncontrolled hypertension.
- The presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
- Cyclophosphamide allergy (Cohort 6 only).
- Pregnancy.
- Breastfeeding.
- Prior T4 immunotherapy.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Clinical Research Facility, Guy's Hospital
London, London, SE1 9RT
John Maher
About this study
The overall goal of this study is to investigate the safety of T4 immunotherapy when administered to treat loco-regional disease in Squamous Cell Cancer of the Head and Neck (SCCHN) that is not suitable for conventional active therapy.
The investigators propose to conduct an open-labelled, non-randomized, dose-escalation phase I trial in which autologous T4+ T-cells are administered to patients with SCCHN. T-cells will be engineered to express a second generation chimeric antigen receptor (CAR) named T1E28z. Engineered T-cells will be injected directly into the tumour site. Patients will not be lymphodepleted. A classical 3+3 design will be employed, with dose escalation from 10^7 through to 10^9 transduced T4+ T-cells, dependent upon toxicity monitoring. It is anticipated that up to 30 patients will be enrolled over the course of the study.
Read the detailed description
Further information is provided in van Schalkwyk MC, Papa SE, Jeannon JP, Guerrero Urbano T, Spicer JF, Maher J. Design of a phase I clinical trial to evaluate intratumoral delivery of ErbB-targeted chimeric antigen receptor T-cells in locally advanced or recurrent head and neck cancer. Hum Gene Ther Clin Dev. 2013 Sep;24(3):134-42. doi: 10.1089/humc.2013.144. PubMed ID: 24099518
- Conditions
- Head and Neck Cancer
- Being tested
- Intra-tumoral T4 immunotherapy
- Keywords
- Chimeric antigen receptor, Immunotherapy, Head and Neck Cancer, Phase I trial, Maximum tolerated dose
- Medical subject headings
- Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intra-tumoral T4 immunotherapyOther
Also called 4ab T1E28z positive T-cells
Intra-tumoral administration of a single dose of T4-positive patient-derived T-cells (at five escalating dose levels) contained within 1-4 mL. Cohort 6 patients receive CAR T-cells (dose level 3) after lymphodepletion with fludarabine and cyclophosphamide. Cohort 7-8 patients receive T4 cells after lymphodepletion as above, combined with 4 doses of nivolumab.
| Study group | Role | What they receive |
|---|---|---|
| Intra-tumoral T4 immunotherapy | Experimental | Treatment arms comprise escalating doses of T4 immunotherapy, administered alone or in combination with lymph-depleting chemotherapy Receives: Other: Intra-tumoral T4 immunotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicities for T4 immunotherapy in SCCHN and determine a safe and feasible recommended dose for phase II testing of intra-tumoral T4 immunotherapy.
Patients will be monitored intensely for the first 24 hours post T4 administration. Patients will the be assessed for signs of toxicity on days 3-4, 5-7, 8, 15, 29 and 43.
Measured: Up to 6 weeks post T4 administration
Secondary outcomes (6)
To investigate serum cytokine levels after administration of T4 immunotherapy
Measured: up to 6 weeks post T4 administration
To investigate persistence of T4+ T-cells at the site of administration and in the peripheral circulation
Measured: up to 6 weeks post T4 administration
To achieve preliminary assessment of anti-tumour activity, using cross-sectional imaging to quantify objective responses
Measured: up to 6 weeks post T4 administration
To investigate tumour ErbB receptor phenotype, before and after administration of T4 immunotherapy
Measured: up to 6 weeks post T4 administration
To investigate immunomodulatory effects of metronomic cyclophosphamide on T4 immunotherapy
Pre- and post-treatment absolute number of circulating T-regulatory cells will be compared.
Measured: up to 6 weeks post T4 administration
To investigate effect of T4 immunotherapy upon immune reactivity against endogenous tumour antigens
ELISPOT will be performed on blood samples taken 3 days prior and 29 days after T4 administration to measure for MAGE-reactive T-cells.
Measured: up to 6 weeks post T4 administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2013 (estimated)
- Study startJun 2015
- Primary completionDec 2024 (estimated)
- Study completionJan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Head and Neck CancerStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- In this dose escalation study, the intervention consists of intratumoral delivery of panErbB-specific CAR T cells, administered alone or following lymphodepleting chemotherapy with fludarabine and cyclophosphamide. In cohort 7, patients will also receive 3 doses of Nivolumab, the first of which is administered 24h before CAR T-cells This note has been added in response to the warning " WARNING: Phase 1/Phase 2 studies typically have at least one Intervention Type of Drug, Biological/Vaccine or Combination Product."
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Collaborators
- Guy's and St Thomas' NHS Foundation Trust
- Responsible party
- Principal investigator, John Maher, King's College London
- Investigators
- John Maher, MD PhD, Principal investigator, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01818323
- Sponsor's protocol ID
- 2012-001654-25
- Status last verified
- Mar 2024
- First submitted
- 19 Mar 2013
- Last updated
- 9 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Davies DM, Foster J, Van Der Stegen SJ, Parente-Pereira AC, Chiapero-Stanke L, Delinassios GJ, Burbridge SE, Kao V, Liu Z, Bosshard-Carter L, Van Schalkwyk MC, Box C, Eccles SA, Mather SJ, Wilkie S, Maher J. Flexible targeting of ErbB dimers that drive tumorigenesis by using genetically engineered T cells. Mol Med. 2012 May 9;18(1):565-76. doi: 10.2119/molmed.2011.00493.
PubMed 22354215Wilkie S, Burbridge SE, Chiapero-Stanke L, Pereira AC, Cleary S, van der Stegen SJ, Spicer JF, Davies DM, Maher J. Selective expansion of chimeric antigen receptor-targeted T-cells with potent effector function using interleukin-4. J Biol Chem. 2010 Aug 13;285(33):25538-44. doi: 10.1074/jbc.M110.127951. Epub 2010 Jun 18.
PubMed 20562098van Schalkwyk MC, Papa SE, Jeannon JP, Guerrero Urbano T, Spicer JF, Maher J. Design of a phase I clinical trial to evaluate intratumoral delivery of ErbB-targeted chimeric antigen receptor T-cells in locally advanced or recurrent head and neck cancer. Hum Gene Ther Clin Dev. 2013 Sep;24(3):134-42. doi: 10.1089/humc.2013.144.
PubMed 24099518
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial: T4 Immunotherapy of Head and Neck Cancer
- ClinicalTrials.gov ID
- NCT01818323
- Acronym / sponsor ID
- 2012-001654-25
- Conditions
- Head and Neck Cancer
- Keywords
- Chimeric antigen receptor, Immunotherapy, Head and Neck Cancer, Phase I trial, Maximum tolerated dose
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Collaborators
- Guy's and St Thomas' NHS Foundation Trust
- Study start
- Jun 2015
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Jan 2025 (estimated)
- First posted
- 26 Mar 2013 (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.
The overall goal of this study is to investigate the safety of T4 immunotherapy when administered to treat loco-regional disease in Squamous Cell Cancer of the Head and Neck (SCCHN) that is not suitable for conventional active therapy.
The investigators propose to conduct an open-labelled, non-randomized, dose-escalation phase I trial in which autologous T4+ T-cells are administered to patients with SCCHN. T-cells will be engineered to express a second generation chimeric antigen receptor (CAR) named T1E28z. Engineered T-cells will be injected directly into the tumour site. Patients will not be lymphodepleted. A classical 3+3 design will be employed, with dose escalation from 10^7 through to 10^9 transduced T4+ T-cells, dependent upon toxicity monitoring. It is anticipated that up to 30 patients will be enrolled over the course of the study.
Detailed description
Further information is provided in van Schalkwyk MC, Papa SE, Jeannon JP, Guerrero Urbano T, Spicer JF, Maher J. Design of a phase I clinical trial to evaluate intratumoral delivery of ErbB-targeted chimeric antigen receptor T-cells in locally advanced or recurrent head and neck cancer. Hum Gene Ther Clin Dev. 2013 Sep;24(3):134-42. doi: 10.1089/humc.2013.144. PubMed ID: 24099518
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- In this dose escalation study, the intervention consists of intratumoral delivery of panErbB-specific CAR T cells, administered alone or following lymphodepleting chemotherapy with fludarabine and cyclophosphamide. In cohort 7, patients will also receive 3 doses of Nivolumab, the first of which is administered 24h before CAR T-cells This note has been added in response to the warning " WARNING: Phase 1/Phase 2 studies typically have at least one Intervention Type of Drug, Biological/Vaccine or Combination Product."
| Arm | Type | Receives |
|---|---|---|
| Intra-tumoral T4 immunotherapy | Experimental | Other: Intra-tumoral T4 immunotherapyTreatment arms comprise escalating doses of T4 immunotherapy, administered alone or in combination with lymph-depleting chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically and/ or cytologically confirmed SCCHN.
- 18 years or older.
- Locally advanced and/ or recurrent head and neck cancer with or without metastatic disease (excluding brain metastases) for whom no standard therapy remains or is suitable.
- Regarding previous treatment, patients may have received prior systemic therapy, including platinum chemotherapy, at least one month earlier. In the presence of metastatic disease, recent short-course palliative radiotherapy to non-target site(s) is allowed.
- Those who refuse palliative treatment may be eligible for participation. However, their reasons for not opting for palliative treatment must be explored thoroughly.
Key exclusion criteria (13 listed)
- The presence of or imminent occurrence of airway obstruction, unless tracheostomy in place.
- The presence of or imminent occurrence of tumour-mediated infiltration of major blood vessels.
- Positive history of HIV-1, HIV-2, HTLV-1, HTLV-2, Hepatitis B, Hepatitis C or syphilis infection.
- Prior splenectomy.
- Clinically active autoimmune disease. Sub-clinical or quiescent autoimmune disease does not exclude from participation.
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 |
|---|---|---|
| Intra-tumoral T4 immunotherapyAlso: 4ab T1E28z positive T-cellsIntra-tumoral administration of a single dose of T4-positive patient-derived T-cells (at five escalating dose levels) contained within 1-4 mL. Cohort 6 patients receive CAR T-cells (dose level 3) after lymphodepletion with fludarabine and cyclophosphamide. Cohort 7-8 patients receive T4 cells after lymphodepletion as above, combined with 4 doses of nivolumab. | Other | Intra-tumoral T4 immunotherapy |
Primary outcome
Dose limiting toxicities for T4 immunotherapy in SCCHN and determine a safe and feasible recommended dose for phase II testing of intra-tumoral T4 immunotherapy.
Time frame: Up to 6 weeks post T4 administration
Patients will be monitored intensely for the first 24 hours post T4 administration. Patients will the be assessed for signs of toxicity on days 3-4, 5-7, 8, 15, 29 and 43.
6 secondary outcomes
To investigate serum cytokine levels after administration of T4 immunotherapy
Time frame: up to 6 weeks post T4 administration
To investigate persistence of T4+ T-cells at the site of administration and in the peripheral circulation
Time frame: up to 6 weeks post T4 administration
To achieve preliminary assessment of anti-tumour activity, using cross-sectional imaging to quantify objective responses
Time frame: up to 6 weeks post T4 administration
To investigate tumour ErbB receptor phenotype, before and after administration of T4 immunotherapy
Time frame: up to 6 weeks post T4 administration
To investigate immunomodulatory effects of metronomic cyclophosphamide on T4 immunotherapy
Time frame: up to 6 weeks post T4 administration
To investigate effect of T4 immunotherapy upon immune reactivity against endogenous tumour antigens
Time frame: up to 6 weeks post T4 administration
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2024.
- Background: PubMed 22354215Davies DM, Foster J, Van Der Stegen SJ, Parente-Pereira AC, Chiapero-Stanke L, Delinassios GJ, Burbridge SE, Kao V, Liu Z, Bosshard-Carter L, Van Schalkwyk MC, Box C, Eccles SA, Mather SJ, Wilkie S, Maher J. Flexible targeting of ErbB dimers that drive tumorigenesis by using genetically engineered T cells. Mol Med. 2012 May 9;18(1):565-76. doi: 10.2119/molmed.2011.00493.
- Background: PubMed 20562098Wilkie S, Burbridge SE, Chiapero-Stanke L, Pereira AC, Cleary S, van der Stegen SJ, Spicer JF, Davies DM, Maher J. Selective expansion of chimeric antigen receptor-targeted T-cells with potent effector function using interleukin-4. J Biol Chem. 2010 Aug 13;285(33):25538-44. doi: 10.1074/jbc.M110.127951. Epub 2010 Jun 18.
- Background: PubMed 24099518van Schalkwyk MC, Papa SE, Jeannon JP, Guerrero Urbano T, Spicer JF, Maher J. Design of a phase I clinical trial to evaluate intratumoral delivery of ErbB-targeted chimeric antigen receptor T-cells in locally advanced or recurrent head and neck cancer. Hum Gene Ther Clin Dev. 2013 Sep;24(3):134-42. doi: 10.1089/humc.2013.144.
- Individual participant dataSharing planned: Yes
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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.
John Maher, MD PhD principal investigator
King's College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Intra-tumoral T4 immunotherapy in people with Head and Neck Cancer, run by King's College London at 1 site in United Kingdom.
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 13 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 9 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact John Maher, MD PhD ((+44) 02071881468 ext. 81468, john.maher@kcl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicities for T4 immunotherapy in SCCHN and determine a safe and feasible recommended dose for phase II testing of intra-tumoral T4 immunotherapy. (time frame: Up to 6 weeks post T4 administration). 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 NCT01818323, which also lists 3 linked publications.
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 9 Oct 2024.