E7 TCR Cell Induction Immunotherapy for Stage II and Stage III HPV-Associated Oropharyngeal Cancer

Phase 2

Terminated

Conditions: Oropharyngeal Neoplasms
Papillomavirus Infections

Interventions: Biological: E7 T-Cell Receptor (TCR)

Registration Number: NCT04015336

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: Background:

The therapy used in this study is called E7 T-cell receptor (TCR) T cell therapy. This therapy is a type of treatment in which a participant's T cells (a type of immune system cell) are changed in the laboratory to attack cancer cells. This treatment might help people with human papillomavirus (HPV)-associated oropharyngeal cancer. Oropharyngeal cancer is a type of head and neck cancer that happens in the oropharynx (the part of the throat at the back of the mouth, including the soft palate, the base of the tongue, and the tonsils). Certain types of the HPV virus can cause this kind of cancer. This study is looking at treatments for cancer caused by HPV-16.

Objective:

The purpose of this study is to determine if E7 TCR T cells can be given safely without delaying standard treatment for HPV-16 associated oropharyngeal cancer. Standard treatment may be surgery or radiation therapy with chemotherapy.

Eligibility: People ages 18 and older with Stage II or III HPV-16 associated oropharyngeal cancer

Design:

Participants will be screened with HLA typing (a blood test needed for eligibility) and HPV testing of the cancer tumor (to determine if the cancer is HPV-16 positive). A new biopsy may be needed if tumor from an outside location is not available for HPV testing. Eligible participants will come to the National Institutes of Health (NIH) campus to have a screening evaluation which will include physical exam, review of medical history and current medications, blood and heart tests, imaging (X-ray, computed tomography (CT) scan, magnetic resonance imaging (MRI) or positron emission tomography (PET) scan), and evaluation of participant's veins that are used for drawing blood.

If the participant is eligible for the study based on the screening evaluation, they will have a baseline evaluation prior to receiving the experimental treatment. The baseline evaluation may include additional laboratory or imaging tests.

Participants will have a large intravenous (IV) catheter inserted into a vein to undergo a procedure called leukapheresis. Leukapheresis is the removal of the blood by a machine to collect specific blood cells. The remaining blood is returned to the body. This procedure is needed to collect the cells that will be modified to target the cancer. These cells will be grown in the lab and given back to the participant through an IV. It takes 11-15 days to grow the cells.

While the cells are growing, the participant will be admitted to the hospital about one week before cell infusion. They will receive 2 types of chemotherapy through an IV catheter over 5 days. The main purpose of the chemotherapy is to make the cells more effective in fighting the cancer tumors. The cells will be given through an IV catheter 1-3 days after the last dose of chemotherapy. Within 24 hours after the cell infusion, participants will be given a cell growth factor called aldesleukin through an IV. Aldesleukin is thought to help the cells live longer in the participant s body. Participants will recover in the hospital until they are well enough to go home. This is usually about 7-12 days after the cell infusion or last dose of aldesleukin.

Participants will have follow-up visits starting every 2 weeks after the date of cell infusion. These will be visits to monitor the safety of the treatment and to evaluate the response of the cancer to the treatment. These visits will continue if the cancer is shrinking. The participant will go back to their local cancer doctor for further care if the cancer stops shrinking, goes away completely or gets bigger.

Participants will have blood drawn periodically to test if the cells have grown or changed. These blood tests will take place immediately before the cells are given, and then at 3, 6, 12 months for the first year and then annually. These tests can be drawn locally and sent to the NIH. Participants will be asked to return to the NIH annually for a physical examination for 5 years after they receive the cells. After that time, participants will be asked to fill-out a questionnaire for the next ten years, for a total follow-up period of 15 years.

Detailed Description: Background:

* Human papillomavirus (HPV)+ oropharyngeal cancer is an increasingly common type of cancer that frequently affects young patients.

* The treatment for locoregionally advanced cancer carries substantial life-long morbidity.

* Although the overall prognosis for HPV+ oropharyngeal cancer is favorable, about 20 percent of patients with stage II disease and 35 percent of patients with stage III disease will die within five years.

* Induction therapy is an area of active study in this type of cancer. The aims of induction therapy are to reduce the risk of disease recurrence and potentially to permit the study of de-intensified definitive treatment of locoregional disease.

* E7 T-cell receptor (TCR) T cells, administered as a single infusion, have demonstrated safety and clinical activity in treatment-refractory metastatic HPV+ cancers.

Objectives:

-To determine the feasibility of systemic treatment with E7 TCR T cells for stage II or stage III HPV+ oropharyngeal cancer.

Eligibility:

* Patients greater than or equal to 18 years old with stage II or stage III HPV+ oropharyngeal cancer.

* The cancer must be HPV16+ and patient must be human leukocyte antigen-A (HLA-A) 02:01+ HLA type.

* Patients must be treatment-naive.

Design:

* This is a phase II, single arm, feasibility study of induction E7 TCR T cell therapy.

* Patients will receive a conditioning regimen of cyclophosphamide and fludarabine, a single infusion of E7 TCR T cells, and systemic aldesleukin.

* Patients will be referred for standard of care definitive therapy (chemoradiation or surgery) at the time of maximum tumor response

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 1-3x10^10 E7 T-Cell Receptor (TCR) T cells	E7 T-Cell Receptor (TCR)	Up to 3x10\^10 E7 T-Cell Receptor (TCR) T cells (based on the number of cells that can be generated in the shortened manufacturing process) will be administered intravenously over 20 to 30 minutes on day 0.

Primary Outcome Measures

Name	Time	Method
Fraction of Participants Who Can Receive Induction Therapy With E7 T-Cell Receptor (TCR) Cells Without Failing the Feasibility Criteria	3 months	Fraction of participants who can receive induction therapy with E7 T-Cell receptor (TCR) cells without failing the feasibility criteria with 95% confidence intervals. The feasibility criteria is defined as follows, 1) delivery of the E7 TCR T Cell induction therapy without an increase in tumor T or N stage between baseline and the last response assessment before referral for definitive treatment, 2) initiation of definitive therapy without a delay in treatment related to toxicity of the induction therapy, and 3) if any participant starts the conditioning regimen chemotherapy but does not receive the E7 TCR T Cells it will be considered a feasibility failure. Failure by one criterion will be scored as a feasibility failure.

Secondary Outcome Measures