Phase I Trial: T4 Immunotherapy of Head and Neck Cancer

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.
13. Eligible for NHS care in the UK.

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.