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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
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

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.

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 65 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 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

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 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 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.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Histologically or cytologically confirmed stage II or stage III (AJCC 8th edition) oropharyngeal squamous cell carcinoma that has not been treated.
  • HPV16+ tumor and HLA-A 02:01+ HLA type (HLA-A 02 is also acceptable for determination of eligibility).
  • Measurable disease by RECIST 1.1 criteria.
  • Patient age from 18 to 70 years. Because no dosing or adverse event data are currently available on the use of E7 TCR T Cells in patients <18 years of age, children are excluded from this study. This reflects the age range of patients with the disease being studied.
  • ECOG performance status 0 or 1.
  • Women of child-bearing potential must have a negative pregnancy test because E7 TCR T Cells have unknown potential for teratogenic or abortifacient effects. Women of child-bearing potential are defined as all women who are not post-menopausal or who have not had a hysterectomy. Postmenopausal will be defined as women over the age of 55 who have not had a menstrual period in at least 1 year.
  • The effects of E7 TCR T Cells on the developing human fetus are unknown. For this reason and because the chemotherapy agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (intrauterine device, hormonal or barrier method of birth control; abstinence; tubal ligation or vasectomy) prior to study entry and for four months after treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Seronegative for HIV antibody. The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment.
  • Seronegative for hepatitis B antigen and hepatitis C antibody. If hepatitis C antibody test is positive, then the patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
  • Must be willing to participate in Gene Therapy Long Term Followup Protocol (15-C-0141), which will follow patients for up to 15 years per Food and Drug Administration (FDA) requirements.
  • Patients must have organ and marrow function as defined below:

    • leukocytes- greater than or equal to 3,000/mcL
    • absolute neutrophil count- greater than or equal to 1,000/mcL
    • platelets- greater than or equal to 100,000/mcL
    • hemoglobin- greater than or equal to 9.0 g/dL
    • total bilirubin- within normal institutional limits except in patients with Gilbert s Syndrome who must have a total bilirubin < 3.0 mg/dL
    • AST(SGOT)/ALT(SGPT)- Serum ALT/AST < 3 times ULN
    • creatinine clearance- Calculated creatinine clearance (CrCl) >50mL/min/1.73m2 for patients with creatinine levels above institutional normal (by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation)
  • Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

  • Patients who are receiving any other investigational agents.
  • History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations at the time of treatment that would limit compliance with study requirements.
  • There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with E7 TCR T Cells. For this reason, women may not breastfeed while receiving study treatment and for one year after the study treatment ends. These potential risks may also apply to other agents used in this study.
  • Patients with any form of systemic immunodeficiency, including acquired deficiency such as HIV or primary immunodeficiency such as Severe Combined Immunodeficiency Disease, are ineligible. The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the treatment.
  • Current use of immunosuppressive medication, EXCEPT for the following:

    • Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
    • Systemic corticosteroids at physiologic doses less than equal to 10 mg/day of prednisone or equivalent;
    • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • Patients with autoimmune diseases such as Crohn s disease, ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis, autoimmune pancreatitis, or systemic lupus erythematosus. Hypothyroidism, vitiligo and other minor autoimmune disorders are not exclusionary.
  • Patients with a second active invasive cancer are not eligible if it may confound assessment of response to the current therapy.
  • Patients who do not have a local physician to provide standard therapy post treatment.

Information from the National Library of Medicine

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


Contacts
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Contact: Erin W Ferraro, R.N. (833) 815-0387 erin.ferraro@nih.gov

Locations
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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      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Christian S Hinrichs, M.D. National Cancer Institute (NCI)

Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04015336     History of Changes
Other Study ID Numbers: 190122
19-C-0122
First Posted: July 11, 2019    Key Record Dates
Last Update Posted: September 13, 2019
Last Verified: August 27, 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
T Cell Receptor
Fludarabine
Cyclophosphamide
Immunotherapy
Aldesleukin
Additional relevant MeSH terms:
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Papillomavirus Infections
Oropharyngeal Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Immunologic Factors
Physiological Effects of Drugs