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Trial record 21 of 30048 for:    Immunologic Factors

A Phase II Study of Neoadjuvant E7 TCR T Cell Immunotherapy for Borderline Resectable and Unresectable Stage I HPV-Associated Oropharyngeal Cancer

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ClinicalTrials.gov Identifier: NCT04044950
Recruitment Status : Not yet recruiting
First Posted : August 5, 2019
Last Update Posted : September 18, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

  • Human papillomavirus (HPV)+ oropharyngeal cancer is an increasingly common type of cancer that frequently affects young patients.
  • Although the prognosis of early-stage cancer is favorable, the treatments can result in significant life-long morbidity.
  • Neoadjuvant therapy is an active area of investigation. The goal of neoadjuvant therapy in this setting is to reduce the risk of disease recurrence and permit the study of de- intensified definitive treatment of early-stage disease.
  • E7 TCR T cells have demonstrated safety and clinical activity in treatment-refractory metastatic HPV+ cancers.

Objectives:

- To determine the feasibility of intratumoral injection of E7 TCR T cells as neoadjuvant therapy for borderline resectable and unresectable stage I HPV+ oropharyngeal cancer.

Eligibility:

- Patients greater than or equal to 18 years of age with borderline resectable or unresectable stage I HPV+ oropharyngeal cancer.

Design:

  • This is a phase II, single arm, feasibility study of neoadjuvant E7 TCR T cell therapy for borderline resectable and unresectable stage I HPV+ oropharyngeal cancer.
  • Patients will receive intratumoral injection of E7 TCR T cells into the primary tumor and palpable lymph nodes
  • Patients will not receive a conditioning chemotherapy regimen or systemic aldesleukin
  • Patients will be referred for definitive standard of care therapy following completion of protocol therapy

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.
  • Although the prognosis of early-stage cancer is favorable, the treatments can result in significant life-long morbidity.
  • Neoadjuvant therapy is an active area of investigation. The goal of neoadjuvant therapy in this setting is to reduce the risk of disease recurrence and permit the study of de- intensified definitive treatment of early-stage disease.
  • E7 TCR T cells have demonstrated safety and clinical activity in treatment-refractory metastatic HPV+ cancers.

Objectives:

- To determine the feasibility of intratumoral injection of E7 TCR T cells as neoadjuvant therapy for borderline resectable and unresectable stage I HPV+ oropharyngeal cancer.

Eligibility:

- Patients greater than or equal to 18 years of age with borderline resectable or unresectable stage I HPV+ oropharyngeal cancer.

Design:

  • This is a phase II, single arm, feasibility study of neoadjuvant E7 TCR T cell therapy for borderline resectable and unresectable stage I HPV+ oropharyngeal cancer.
  • Patients will receive intratumoral injection of E7 TCR T cells into the primary tumor and palpable lymph nodes
  • Patients will not receive a conditioning chemotherapy regimen or systemic aldesleukin
  • Patients will be referred for definitive standard of care therapy following completion of protocol therapy

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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 Neoadjuvant E7 TCR T Cell Immunotherapy for Borderline Resectable and Unresectable Stage I HPV-Associated Oropharyngeal Cancer
Estimated Study Start Date : September 23, 2019
Estimated Primary Completion Date : July 3, 2023
Estimated Study Completion Date : December 2, 2024

Arm Intervention/treatment
Experimental: Arm 1
Approximately 3x108 E7 TCR T cells (based on the number of disease sites the patient has) will be injected on day 0.
Biological: E7 TCR
The injection will be approximately 3x10^8 E7 TCR T cells, unless fewer cells are generated, at each site of organ involvement (i.e. primary tumor, palpable lymph node (s)) in approximately 1-2 ml of volume.




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 three 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 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Histologically or cytologically confirmed stage I (AJCC 8th edition) oropharyngeal squamous cell carcinoma that has not been treated.
  • HPV16+ tumor and HLA-A*02:01+ HLA type (p16+ by THC and HLA-A*02 is also acceptable for enrollment but not for treatment).
  • Borderline/marginally resectable or unresectable oropharyngeal cancer. Resectability will be determined by the referring physician and confirmed by otolaryngologists at the NTH (confirmation is not needed for enrollment but is required prior to treatment.
  • Measurable disease by RECTST v1.1 criteria.
  • Patient age greater than 18 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.
  • ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).
  • Patients must have normal organ and marrow function as defined below:

    • leukocytes greater than or equal to 3,000/mcL
    • absolute neutrophil count greater than or equal to 1,500/mcL
    • platelets greater than or equal to 100,000/mcL
    • total bilirubin within normal institutional limits
    • AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of normal
    • creatinine within normal institutional limits OR
    • creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal.
  • Women of child-bearing potential must have a negative pregnancy test. 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, 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 up to 4 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 Follow-up Protocol (15C0141), which will follow patients for up to 15 years per Food and Drug Administration (FDA) requirements.
  • 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.
  • 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.
  • Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with E7 TCR T cells, breastfeeding should be discontinued if the mother is treated with E7 TCR T cells.
  • 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.
  • Patients on immunosuppressive drugs.
  • Concurrent systemic steroid therapy if greater than the equivalent of 5 mg prednisone PO daily. Patients previously on steroids must be off steroids for four weeks prior to treatment.
  • Patients with active cardiac ischemia or severe chronic obstructive pulmonary disease are not eligible.
  • 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 cellular 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): NCT04044950


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: NCT04044950     History of Changes
Other Study ID Numbers: 190130
19-C-0130
First Posted: August 5, 2019    Key Record Dates
Last Update Posted: September 18, 2019
Last Verified: July 29, 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) ):
Intratumoral Injection
Biomarkers
T Cell Receptor
Immunotherapy
Neoadjuvant therapy
Additional relevant MeSH terms:
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Immunologic Factors
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
Physiological Effects of Drugs