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

Uterine Cervical Neoplasms Clinical Trial

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

Status Terminated

Clinical Trial 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....

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Uterine Cervical Neoplasms

• NCT number: NCT04476251
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Terminated
• Phase: Early Phase 1
• Start date: January 14, 2021
• Completion date: September 15, 2021