Phase I Trial: T4 Immunotherapy of Head and Neck Cancer

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2013 by King's College London
Sponsor:
Collaborator:
Guy's and St Thomas' NHS Foundation Trust
Information provided by (Responsible Party):
John Maher, King's College London
ClinicalTrials.gov Identifier:
NCT01818323
First received: March 19, 2013
Last updated: March 25, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Other: Intra-tumoral T4 immunotherapy
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Phase I Trial: T4 Immunotherapy of Head and Neck Cancer

Resource links provided by NLM:


Further study details as provided by King's College London:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • To investigate serum cytokine levels after administration of T4 immunotherapy [ Time Frame: up to 6 weeks post T4 administration ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • To investigate tumour ErbB receptor phenotype, before and after administration of T4 immunotherapy [ Time Frame: up to 6 weeks post T4 administration ] [ Designated as safety issue: No ]
  • To investigate immunomodulatory effects of metronomic cyclophosphamide on T4 immunotherapy [ Time Frame: up to 6 weeks post T4 administration ] [ Designated as safety issue: Yes ]
    Pre- and post-treatment absolute number of circulating T-regulatory cells will be compared.

  • To investigate effect of T4 immunotherapy upon immune reactivity against endogenous tumour antigens [ Time Frame: up to 6 weeks post T4 administration ] [ Designated as safety issue: No ]
    ELISPOT will be performed on blood samples taken 3 days prior and 29 days after T4 administration to measure for MAGE-reactive T-cells.


Estimated Enrollment: 30
Study Start Date: June 2013
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intra-tumoral T4 immunotherapy Other: Intra-tumoral T4 immunotherapy
Intra-tumoral administration of T4-positive patient-derived T-cells contained within 1 mL.
Other Name: 4ab T1E28z positive T-cells

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically and/ or cytologically confirmed SCCHN.
  2. 18 years or older.
  3. 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.
  4. 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.
  5. Those who refuse palliative treatment may be eligible for participation. However, their reasons for not opting for palliative treatment must be explored thoroughly.
  6. 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.
  7. Eastern Co-operative Oncology Performance Status of 0-2.
  8. 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.
  9. Haematology results within seven days of enrolment: neutrophils >1.5 x 109/L, platelets >100 x 109/L, haemoglobin >9g/dl, INR <1.5.
  10. 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)
  11. 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.
  12. Written informed consent prior to registration.

Exclusion Criteria:

  1. The presence of or imminent occurrence of airway obstruction, unless tracheostomy in place.
  2. The presence of or imminent occurrence of tumour-mediated infiltration of major blood vessels.
  3. Positive history of HIV-1, HIV-2, HTLV-1, HTLV-2, Hepatitis B, Hepatitis C or syphilis infection.
  4. Prior splenectomy.
  5. Clinically active autoimmune disease. Sub-clinical or quiescent autoimmune disease does not exclude from participation.
  6. Treatment in the preceding week with systemic corticosteroids (> 20mg prednisolone/ day), any systemic immunomodulatory agent, radiotherapy, chemotherapy or investigational medicinal product.
  7. Concurrent use of anticoagulant therapy is not permissible.
  8. 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.
  9. The presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
  10. Cyclophosphamide allergy (Cohort 6 only).
  11. Pregnancy.
  12. Breastfeeding.
  13. Prior T4 immunotherapy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01818323

Contacts
Contact: John Maher, MD PhD (+44) 02071881468 ext 81468 john.maher@kcl.ac.uk

Locations
United Kingdom
Clinical Research Facility, Guy's Hospital Not yet recruiting
London, United Kingdom, SE1 9RT
Principal Investigator: John Maher         
Sponsors and Collaborators
King's College London
Guy's and St Thomas' NHS Foundation Trust
Investigators
Principal Investigator: John Maher, MD PhD King's College London
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: John Maher, Senior Lecturer in Immunology, King's College London
ClinicalTrials.gov Identifier: NCT01818323     History of Changes
Other Study ID Numbers: 2012-001654-25
Study First Received: March 19, 2013
Last Updated: March 25, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by King's College London:
Chimeric antigen receptor
Immunotherapy
Head and Neck Cancer
Phase I trial
Maximum tolerated dose

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on October 23, 2014