T4 immunotherapy for head and neck cancer

Phase I Trial: T4 Immunotherapy of Head and Neck Cancer

This study is testing a new type of immunotherapy for patients with head and neck cancer who can't use standard treatments to see if it's safe and how well it works.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: King's College London (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, cyclophosphamide, chimeric antigen receptor
• Locations: 1 site (London)
• Trial ID: NCT01818323 on ClinicalTrials.gov

What this trial studies

This phase I trial investigates the safety of T4 immunotherapy in patients with squamous cell carcinoma of the head and neck (SCCHN) who are not suitable for conventional therapies. The study employs a non-randomized, dose-escalation design where autologous T4+ T-cells, engineered to express a chimeric antigen receptor, are injected directly into the tumor site. Up to 30 patients will be enrolled, and the maximum tolerated dose will be determined through a classical 3+3 design while monitoring for toxicity. The trial aims to provide insights into the feasibility and safety of this innovative treatment approach.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with locally advanced or recurrent SCCHN who have no suitable standard therapy available.

Not a fit: Patients with brain metastases or those who are not eligible for intra-tumoral injection may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with advanced head and neck cancer who have exhausted standard treatment options.

How similar studies have performed: While this approach is innovative, similar studies using chimeric antigen receptor T-cell therapies have shown promise in other cancer types, indicating potential for success in this context.

Eligibility 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.
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.

Where this trial is running

London

• Clinical Research Facility, Guy's Hospital — London, United Kingdom (Recruiting)

Study contacts

• Principal investigator: John Maher, MD PhD — King's College London
• Study coordinator: John Maher, MD PhD

Conditions Head and Neck Cancer; Chimeric antigen receptor; Immunotherapy; Phase I trial; Maximum tolerated dose