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

Early Phase 1

Terminated

Conditions: Uterine Cervical Neoplasms

Interventions: Biological: E7 T-Cell Receptor (TCR)

Registration Number: NCT04476251

Lead Sponsor: 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 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 1

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 1/E7 T-Cell Receptor (TCR) T Cell Therapy	E7 T-Cell Receptor (TCR)	E7 TCR T Cell Therapy

Primary Outcome Measures

Name	Time	Method
The Fraction of Participants for Whom E7 T-Cell Receptor (TCR) Induction Therapy is Feasible in Participants With Cervical Cancer	6 months	The Fraction of participants for whom E7 T-Cell Receptor (TCR) induction therapy is feasible in participants with cervical cancer

Secondary Outcome Measures

Name	Time	Method
Fraction of Participants With Relapse-free Survival at 2 Years and 5 Years Following Definitive Standard of Care Therapy	2 yrs and 5 yrs	Fraction of participants with relapse-free survival at 2 years and 5 years estimated from a Kaplan-Meier curve of relapsed free survival following definitive standard of care therapy who achieve a success. Relapsed free survival is defined as the time from date on study to date of relapse of disease.
Fraction of Participants With Grade 1-5 Adverse Events	1 year	To evaluate the safety of E7 induction therapy, the types and grades of toxicity obtained will be reported. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.
Percentage of E7 T-Cell Receptor (TCR)T Cells Following Completion of Chemoradiation	1 year	Percentage of E7 T-Cell Receptor (TCR)T cells following completion of chemoradiation
Fraction of Participants Who Achieve an Objective Response (Partial Response + Complete Response) Following E7 T-Cell Receptor (TCR) T Cell Induction Therapy	1 year	Fraction of participants who achieve an objective response (Partial Response + Complete Response) following E7 induction therapy will be reported. Response may be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesion; and/or Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Complete Metabolic Response is complete resolution of F-fluorodeoxyglucose (FDG) uptake in all lesions, and Partial Metabolic Response is ≥ 30% reduction of the SUL (lean body mass corrected standard uptake value) peak and an absolute drop of 0.8 SULpeak units.