E7 TCR Cell Induction Immunotherapy for Stage II and Stage III HPV-Associated Oropharyngeal Cancer
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|ClinicalTrials.gov Identifier: NCT04015336|
Recruitment Status : Not yet recruiting
First Posted : July 11, 2019
Last Update Posted : September 13, 2019
The therapy used in this study is called E7 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 papilloma virus (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.
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 65 with Stage II or III HPV-16 associated oropharyngeal cancer
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 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, CT scan, MRI or 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 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.
|Condition or disease||Intervention/treatment||Phase|
|Papillomavirus Infections Oropharyngeal Neoplasms||Biological: E7 TCR||Phase 2|
- 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 TCR T cells, administered as a single infusion, have demonstrated safety and clinical activity in treatment-refractory metastatic HPV+ cancers.
-To determine the feasibility of systemic treatment with E7 TCR T cells for stage II or stage III HPV+ oropharyngeal cancer.
- Patients greater than or equal to 18 years old and less than or equal to 70 years old with stage II or stage III HPV+ oropharyngeal cancer.
- The cancer must be HPV16+ and patient must be HLA-A 02:01+ HLA type.
- Patients must be treatment-naive.
- 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
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||180 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of E7 TCR T Cell Induction Immunotherapy for Stage II and Stage III HPV-Associated Oropharyngeal Cancer|
|Estimated Study Start Date :||September 18, 2019|
|Estimated Primary Completion Date :||April 28, 2023|
|Estimated Study Completion Date :||April 26, 2024|
Experimental: Arm 1
Up to 3x1010 E7 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.
Biological: E7 TCR
The dose of E7 TCR T cells will be 3 x 1010 TCR+ T cells (unless fewer cells are generated) administered once.
- The fraction who achieve a success among those who receive E7 TCR T cell administration and who can be evaluated for the two feasibility criteria, with 95% confidence intervals on the fraction reported as well. [ Time Frame: 3 months ]The fraction who achieve a success will be determined and reported.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04015336
|Contact: Erin W Ferraro, R.N.||(833) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Not yet recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Christian S Hinrichs, M.D.||National Cancer Institute (NCI)|