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
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.
To find out if people with Stage IIB-IVA cervical cancer can safely be given E7 TCR T cells before they get standard treatment.
People age 18 and older who have Stage IIB-IVA cervical cancer
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|
- 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.
-To determine the feasibility of induction E7 TCR T cell therapy for FIGO (2018) stage IIB-IVA, HPV16+ cervical cancer
- 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).
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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).
- 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
- 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
- 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
- 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
- to assess objective response rate following E7 induction therapy [ Time Frame: 1 year ]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): NCT04476251
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Scott M Norberg, D.O.||National Cancer Institute (NCI)|