NCT04476251

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

A Pilot Study of E7 TCR T Cell Induction Immunotherapy for Stage IIB-IVA Cervical Cancer

• Status: Terminated
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 1 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

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 T-cell receptor (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 hearts 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 National Institutes of Health (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....

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 International Federation of Gynecology and Obstetrics (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 T-cell receptor (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 human papillomavirus 16 (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 loop electrosurgical excision procedure (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.

Conditions

• Uterine Cervical Neoplasms

Interventions

Type	Name	Description
BIOLOGICAL	E7 T-Cell Receptor (TCR)	Patients will receive up to 3x10\^10 E7 T-Cell Receptor (TCR) T cells (i.e. TCR+ cells).

Timeline

• Start date: 2021-01-14
• Primary completion: 2021-09-15
• Completion: 2021-09-15
• First posted: 2020-07-20
• Last updated: 2021-12-15
• Results posted: 2021-12-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study