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Trial Title:
Phase I Trial: T4 Immunotherapy of Head and Neck Cancer
NCT ID:
NCT01818323
Condition:
Head and Neck Cancer
Conditions: Official terms:
Head and Neck Neoplasms
Immunomodulating Agents
Conditions: Keywords:
Chimeric antigen receptor
Immunotherapy
Head and Neck Cancer
Phase I trial
Maximum tolerated dose
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention 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."
Primary purpose:
Treatment
Masking:
None (Open Label)
Masking description:
Open label
Intervention:
Intervention type:
Other
Intervention name:
Intra-tumoral T4 immunotherapy
Description:
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.
Arm group label:
Intra-tumoral T4 immunotherapy
Other name:
4ab T1E28z positive T-cells
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.
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
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Clinical Research Facility, Guy's Hospital
Address:
City:
London
Zip:
SE1 9RT
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
John Maher
Start date:
June 2015
Completion date:
January 2025
Lead sponsor:
Agency:
King's College London
Agency class:
Other
Collaborator:
Agency:
Guy's and St Thomas' NHS Foundation Trust
Agency class:
Other
Source:
King's College London
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT01818323