Trials / Completed

CompletedNCT02858310

E7 TCR T Cells for Human Papillomavirus-Associated Cancers

A Phase I/II Trial of T Cell Receptor Gene Therapy Targeting HPV-16 E7 for HPV-Associated Cancers

Status: Completed
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 224 (actual)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years – 120 Years
Healthy volunteers: Not accepted

Summary

Background: Human papillomavirus (HPV) can cause cervical, throat, anal, and genital cancers. Cancers caused by HPV have an HPV protein called E7 inside of their cells. In this new therapy, researchers take a person's blood, remove certain white blood cells, and insert genes that make them to target cancer cells that have the E7 protein. The genetically changed cells, called E7 T cell receptor (TCR) cells, are then given back to the person to fight the cancer. Researchers want to see if this can help people. Objective: To determine a safe dose and efficacy of E7 TCR cells and whether these cells can help patients. Eligibility: Adults ages 18 and older with an HPV-16-associated cancer, including cervical, vulvar, vaginal, penile, anal, or oropharyngeal. Design: Participants will list all their medicines. Participants will have many screening tests, including imaging procedures, heart and lung tests, and lab tests. They will have a large catheter inserted into a vein. Participants will have leukapheresis. Blood will be removed through a needle in the arm. A machine separates the white blood cells. The rest of the blood is returned through a needle in the other arm. The cells will be changed in the lab. Participants will stay in the hospital. Over several days, they will get: Chemotherapy drugs E7 TCR cells Shots or injections to stimulate the cells Participants will be monitored in the hospital up to 12 days. They will get support medicine and have blood and lab tests. Participants will have a clinic visit about 40 days after cell infusion. They will have a physical exam, blood work, scans, and maybe x-rays. Participants will have many follow-up visits with the same procedures. At some visits, they may undergo leukapheresis. Participants will be followed for 15 years.

Detailed description

Background: * Metastatic or refractory/recurrent human papillomavirus (HPV)-16+ cancers (cervical, vulvar, vaginal, penile, anal, and oropharyngeal cancers) are incurable and poorly palliated by standard therapies. * HPV-16+ cancers constitutively express the HPV-16 E7 oncoprotein, which is absent from healthy human tissues. * Administration of T cell receptor (TCR) gene engineered T cells can induce objective tumor responses in certain malignancies including HPV-16+ cancers. * T cells genetically engineered with a TCR targeting HPV-16 E7 (E7 TCR) display specific reactivity against human leukocyte antigen (HLA)-A2+, HPV-16+ target cells. Objectives: Phase I Primary Objective \- To determine a safe dose for E7 TCR cells plus aldesleukin for the treatment of metastatic HPV-16+ cancers. Phase II Primary Objective -To determine safety and efficacy of E7 TCR cells plus aldesleukin for the treatment of metastatic HPV-16+ cancers. Eligibility: * Patients greater than or equal to 18 years old with metastatic or refractory/recurrent HPV-16+ cancer. * Prior first line systemic therapy is required unless the patient declines standard treatment. * Patients must be HLA-A\*02:01-positive. Design: * This is a phase I/II clinical trial that will test the safety and efficacy of E7 TCR cells. * All patients will receive a non-myeloablative lymphocyte-depleting preparative regimen of cyclophosphamide and fludarabine followed by a single infusion of E7 TCR cells. Cell infusion will be followed by high dose aldesleukin. * Re-enrollment will be allowed for a small number of subjects.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	E7 TCR cells	T cells genetically engineered with a T cell receptor (TCR) targeting human papillomavirus (HPV -16 E7 (E7 TCR) that display specific reactivity against human leukocyte antigen (HLA-A2+, HPV-16+ target cells.
DRUG	Aldesleukin	Following cell infusion, the patient receives high-dose bolus aldesleukin, which is dosed to individual patient tolerance. Aldesleukin improves the survival of E7 T cell receptor (TCR) cells after infusion.
DRUG	Fludarabine	Part of the non-myeloablative lymphocyte-depleting preparative regimen.
DRUG	Cyclophosphamide	Part of the non-myeloablative lymphocyte-depleting preparative regimen.
DIAGNOSTIC_TEST	EKG	Screening/Baseline. Follow-up (end of treatment).
PROCEDURE	Biopsy	Screening/Baseline. Following treatment (6 weeks post treatment preferred) and at disease progression only.
DIAGNOSTIC_TEST	Chest CT and MRI or PET	Screening/Baseline. Follow-up (end of treatment). 40 days (+/- 2 weeks) after cell infusion; additional visits as indicated.
DIAGNOSTIC_TEST	PFT	Screening/Baseline.
DRUG	Granisetron	Supportive medication for nausea/vomiting/anorexia. 0.01 mg/kg intravenous (IV) every(q) day as needed (prn).
DRUG	Ondansetron	Supportive medication for nausea/vomiting/anorexia. Ondansetron 10mg intravenous (IV) every(q) 8 hours(hr) as needed (prn).
DRUG	Droperidol	Supportive medication for nausea/vomiting/anorexia. 1mg intravenous (IV) at 4-6 hours(h) as needed (prn).
DRUG	Prochlorperazine	Supportive medication for nausea/vomiting/anorexia. 25mg per rectum (PR) as needed (prn) or 10mg intravenous (IV) every(q) 6hours(h) prn.
DRUG	Diphenoxylate HCL	Supportive medication for diarrhea. 2.5mg by mouth (po) every(q) 3 hours(h) as needed (prn).
DRUG	Atropine sulfate	Supportive medication for diarrhea. 25mcg by mouth (po) every(q) 3 hours(h) as needed (prn).
DRUG	Codeine sulfate	Supportive medication for diarrhea. 30-60mg by mouth (po) every(q) 4 hours(h) as needed (prn).
DRUG	Loperamide	Supportive medication for diarrhea. 2mg by mouth (po) every(q) 3 hours(h) as needed (prn).
DRUG	Indomethacin	Supportive medication for fever. 50-75mg by mouth (po) every(q) 8 hours(h).
DRUG	Acetaminophen	Supportive medication for fever. 650mg by mouth (po) every 4 hours (q) 4hr.
DRUG	Diphenhydramine HCL	Supportive medication for pruritis. 25-50mg by mouth (po) every 4 hours (q) 4hr as needed (prn).
DRUG	Hydroxyzine HCL	Supportive medication for pruritis. 10-20mg by mouth (po) every 6 hours(h), as needed (prn).
DRUG	Meperidine	Supportive medication for chills. 25-50mg intravenous (IV) every 1 hour (q1hr), as needed (prn).

Timeline

Start date: 2017-01-27
Primary completion: 2025-07-02
Completion: 2025-07-02
First posted: 2016-08-08
Last updated: 2026-03-09
Results posted: 2026-03-09

Locations

2 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT02858310. Inclusion in this directory is not an endorsement.