T4 immunotherapy of head and neck cancer

• Register: ISRCTN
• Last refreshed on: 8 January 2024
• Main ID: ISRCTN81726461
• Date of registration: 15/07/2015
• Prospective Registration: No
• Primary sponsor: King's College London
• Public title: T4 immunotherapy of head and neck cancer
• Scientific title: Phase 1 trial: T4 immunotherapy of head and neck cancer
• Date of first enrolment: 05/06/2015
• Target sample size: 21
• Recruitment status: Ongoing
• URL: https://www.isrctn.com/ISRCTN81726461
• Study type: Interventional
• Study design: Non-randomised; Interventional; Design type: Treatment (Treatment)
• Phase: Phase I

Countries of recruitment

England, United Kingdom

Contacts

• Name: John Maher

Key inclusion & exclusion 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 aquisition (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: neutrophilis >1.5 x 109/L, platelets >100 x 109/L, haemoglobin >9g/dl, INR <1.5
10. Biochemistry results within seven days of enrolment:
10.1. Serum creatinine <1.5 upper limit of normal
10.2. Bilirubin <1.25 times normal
10.3. 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 sterlized, 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 infraction, 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 - Final (sixth) cohort only
11. Pregnancy
12. Prior T4 immunotherapy

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Topic: Cancer; Subtopic: Head and Neck Cancer; Disease: Head and Neck
Cancer

Intervention(s)

Intratumoural T4 immunotherapy, delivered at a single setting to multiple points in a locally advanced or recurrent tumour.
Study Entry : Registration only

Primary Outcome(s)

To define dose limiting toxicities for T4 immunotherapy in SCCHN.

Secondary Outcome(s)

1. To determine a safe and feasible recommended dose for phase II testing of intra-tumoural T4 Immunotherapy
2. To investigate serum cytokine levels after administration of T4 immunotherapy
3. To investigate persistence of T4+ T-cells at the site of administration and in the peripheral circulation
4. To achieve preliminary assessment of anti-tumour activity, using cross-sectional imaging to quantify objective responses
5. To investigate tumour ErbB receptor phenotype, before and after administration of T4 immunotherapy
6. To investigate immunomodulatory effects of low dose cyclophosphamide on T4 immunotherapy.
7. To investigate effect of T4 immunotherapy upon immune reactivity against endogenous tumour antigens

Secondary ID(s)

19183

2012-001654-25

NCT01818323

Source(s) of Monetary Support

Jon Moulton Charitable Foundation, Wellcome Trust

Ethics review

Status:
Approval date:
Contact:

Old ethics approval format; NRES committee west London, 20/11/2012, ref: 12/LO/1834

Results

• Results available: Yes
• Date Completed: 31/12/2024