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E7 TCR T Cell Induction Immunotherapy for Stage IIB-IVA Cervical Cancer

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ClinicalTrials.gov Identifier: NCT04476251
Recruitment Status : Terminated (Multiple logistical challenges)
First Posted : July 20, 2020
Last Update Posted : September 17, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

More than 12,000 cases of cervical cancer are diagnosed in the United States each year. A new therapy has been developed that involves taking white blood cells from a person, genetically modifying the cells in a lab so they recognize cancer, and then giving the cells back to the person. Researchers want to see if this therapy can help people with cervical cancer.

Objective:

To find out if people with Stage IIB-IVA cervical cancer can safely be given E7 TCR T cells before they get standard treatment.

Eligibility:

People age 18 and older who have Stage IIB-IVA cervical cancer

Design:

Participants will be screened under a separate protocol. Tests will include:

  • Physical exam
  • Medicine review
  • Blood tests
  • Pregnancy test (if needed)
  • Vein assessment
  • Tumor sample or biopsy
  • Electrocardiogram (to record the heart s electrical activity)
  • Imaging scans, x-rays, and/or endoscopy
  • Heart and/or lung tests.

Some screening tests will be repeated during the study.

Participants will undergo leukapheresis. For this, blood is removed through a needle in the arm. A machine removes the white blood cells. The rest of the blood is returned through a needle in the other arm. Participants may need to have a large catheter inserted into a vein.

Participants will stay at the hospital for 2-3 weeks. They will get chemotherapy drugs. They will get the E7 TCR T cells as an intravenous infusion. They will get the drug aldesleukin.

Participants will visit the NIH 3 and 6 weeks after treatment. They will be contacted yearly for 5 years. They will be asked to participate in long-term follow-up for 15 years....


Condition or disease Intervention/treatment Phase
Uterine Cervical Neoplasms Biological: E7 TCR Early Phase 1

Detailed Description:

Background:

  • Cervical cancer is the third most common cause of death among women with gynecologic cancers in the United States. Worldwide, cervical cancer accounts for nearly 300,000 deaths annually.
  • Virtually all cases of cervical cancer result from chronic infection with high-risk human papillomavirus (HPV), the most common type being HPV16.
  • The treatment of locally advanced cervical cancer consists of chemoradiation +/- extended field radiation therapy. Participants with FIGO (revised 2018) stage III-IVA have the worse prognosis with approximately 50% of the participants dying from their disease within 5 years.
  • Induction chemotherapy is an active area of study in this type of cancer. The aim of induction therapy is to reduce the risk of disease recurrence and improve overall survival.
  • E7 TCR T cells, administered as a single infusion, have demonstrated safety and clinical activity in advanced, treatment-refractory metastatic HPV+ cancers.

Objectives:

-To determine the feasibility of induction E7 TCR T cell therapy for FIGO (2018) stage IIB-IVA, HPV16+ cervical cancer

Eligibility:

  • Participants greater than or equal to 18 years old with FIGO (2018) stage IIB-IVA cervical cancer.
  • The cancer must be HPV16+ and participant must be HLA-A*02:01+.
  • Participants must be treatment-naive (i.e., no prior local or systemic treatment, including radiation; prior LEEP procedure or cone biopsy is allowed).

Design:

  • This is a single arm, pilot study, testing the feasibility of induction E7 TCR T cell therapy.
  • Participants will receive a conditioning regimen of cyclophosphamide and fludarabine, a single infusion of E7 TCR T cells, and systemic aldesleukin.
  • Participants will be referred for standard of care definitive therapy (i.e., chemoradiation +/- extended field radiation therapy) within 6 weeks after infusion of E7 TCR T cells.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of E7 TCR T Cell Induction Immunotherapy for Stage IIB-IVA Cervical Cancer
Actual Study Start Date : January 14, 2021
Actual Primary Completion Date : September 15, 2021
Actual Study Completion Date : September 15, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cervical Cancer

Arm Intervention/treatment
Experimental: Arm 1
E7 TCR T Cell Therapy
Biological: E7 TCR
Patients will receive up to 3x10^10 E7 TCR T cells (i.e. TCR+ cells).




Primary Outcome Measures :
  1. determine if it is feasible to administer E7 TCR T cells prior to definitive therapy in patients with cervical cancer. [ Time Frame: 6 months ]
    the fraction of subjects for whom E7 TCR induction therapy is feasible


Secondary Outcome Measures :
  1. to assess the relapse-free survival at 2 years and 5 years following definitive standard of care therapy [ Time Frame: 2 yrs and 5 yrs ]
    fraction who achieve a success will be determined and reported

  2. to evaluate the safety of E7 induction therapy [ Time Frame: 1 year ]
    the types and grades of toxicity obtained will be report and findings described. fraction who achieve a success will be determined and reported

  3. to determine the percentage of E7 TCR T cells following completion of chemoradiation [ Time Frame: 1 year ]
    the types and grades of toxicity obtained will be report and findings described. fraction who achieve a success will be determined and reported

  4. to assess objective response rate following E7 induction therapy [ Time Frame: 1 year ]
    fraction who achieve a success will be determined and reported



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

-INCLUSION CRITERIA:

  1. Participants with histologically or cytologically confirmed carcinoma of the cervix that has not been treated, with clinical staging as follows:

    • Lead-in safety cohort: FIGO stage IIIC-IVA (2018 International FIGO Staging System)
    • After lead-in safety cohort: FIGO stage IIB-IVA (2018 International FIGO Staging System)
  2. HPV16+ tumor and HLA-A*02:01+ HLA type. Note: HLA-A*02 is also acceptable for enrollment but not for treatment.
  3. Measurable disease by RECIST 1.1 criteria or PERCIST (if not eligible by RECIST 1.1).
  4. Age 18 years. Because no dosing or adverse event data are currently available on the use of E7 TCR T cells in participants <18 years of age, children are excluded from this study. Note: This age range is consistent with the age of participants with the disease being studied.
  5. ECOG performance status 0 or 1.
  6. 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. Note: Postmenopausal will be defined in this study as women over the age of 55 who have not had a menstrual period in at least 1 year.
  7. 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 must agree to use adequate contraception (e.g., 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 is participating in this study, she should inform her treating physician immediately.
  8. Seronegative for HIV antibody. The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment.
  9. Seronegative for hepatitis B antigen and hepatitis C antibody. If hepatitis C antibody test is positive, then the participant must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
  10. Must be willing to participate in Gene Therapy Long Term Follow up Protocol (20C0051), which will follow participants for up to 15 years per Food and Drug Administration(FDA) requirements.
  11. Participants must have organ and marrow function as defined below:

    • leukocytes >=3,000/mcL
    • absolute neutrophil count >=1,500/mcL
    • platelets >=100,000/mcL
    • hemoglobin >=9.0 g/dL
    • total bilirubin within normal institutional limits except in participants with Gilbert s Syndrome who must have a total bilirubin < 3.0 mg/dL
    • AST(SGOT)/ALT(SGPT) Serum ALT/AST < 2.5X ULN
    • creatinine clearance Calculated creatinine clearance (CrCl) >=50 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal (by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation)
  12. Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

  1. Previous treatment for invasive cervical cancer including:

    • Chemotherapy or other systemic treatments
    • Radiation therapy
    • Hysterectomy (prior LEEP procedure or cone biopsy is allowed)
  2. Participants who are receiving any other investigational agents.
  3. History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study.
  4. 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.
  5. 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. These potential risks may also apply to other agents used in this study.
  6. Participants 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. Participants who have decreased immune competence may be less responsive to the treatment.
  7. Participants on immunosuppressive drugs including corticosteroids.
  8. Participants 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.
  9. Participants with a second invasive malignancy requiring treatment within the last 2 years are not eligible with the following exceptions:

    • Ductal carcinoma in situ (DCIS) of the breast
    • Cutaneous skin cancers requiring only local excision

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): NCT04476251


Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Scott M Norberg, D.O. National Cancer Institute (NCI)
Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04476251    
Other Study ID Numbers: 200116
20-C-0116
First Posted: July 20, 2020    Key Record Dates
Last Update Posted: September 17, 2021
Last Verified: September 2021

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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
Immunotherapy
Aldesleukin
Cyclophosphamide
Fludarabine
Additional relevant MeSH terms:
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Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases