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

NCT04476251 | Terminated Early Phase 1 Results FDA Drug

• 2 other identifiers: 20011620-C-0116
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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....

Conditions

Uterine Cervical Neoplasms

Keywords

T Cell Receptor; Immunotherapy; Aldesleukin; Cyclophosphamide; Fludarabine

Outcome Measures

Primary Outcomes (1)

• The Fraction of Participants for Whom E7 T-Cell Receptor (TCR) Induction Therapy is Feasible in Participants With Cervical Cancer

  The Fraction of participants for whom E7 T-Cell Receptor (TCR) induction therapy is feasible in participants with cervical cancer

  6 months

Secondary Outcomes (4)

• 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 Grade 1-5 Adverse Events

  1 year

• Percentage of E7 T-Cell Receptor (TCR)T Cells Following Completion of Chemoradiation

  1 year

• Fraction of Participants Who Achieve an Objective Response (Partial Response + Complete Response) Following E7 T-Cell Receptor (TCR) T Cell Induction Therapy

  1 year

Other Outcomes (1)

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Date treatment consent signed to date off study, approximately 20 days.

Study Arms (1)

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

EXPERIMENTAL

E7 TCR T Cell Therapy

Biological: E7 T-Cell Receptor (TCR)

Interventions

E7 T-Cell Receptor (TCR) BIOLOGICAL

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

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

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with histologically or cytologically confirmed carcinoma of the cervix that has not been treated, with clinical staging as follows:
• Lead-in safety cohort: FIGO (International Federation of Gynecology and Obstetrics) stage IIIC-IVA (2018 International FIGO Staging System)
• After lead-in safety cohort: FIGO stage IIB-IVA (2018 International FIGO Staging System)
• Human papillomavirus 16 (HPV16+) tumor and HLA-A\*02:01+ Human leukocyte antigen (HLA) type. Note: HLA-A\*02 is also acceptable for enrollment but not for treatment.
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria or Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) (if not eligible by RECIST 1.1).
• Age 18 years. Because no dosing or adverse event data are currently available on the use of E7 TCR T cells in participants \<18 years of age, children are excluded from this study. Note: This age range is consistent with the age of participants with the disease being studied.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Women of child-bearing potential must have a negative pregnancy test because E7 TCR T cells have unknown potential for teratogenic or abortifacient effects. Women of child- bearing potential are defined as all women who are not post-menopausal or who have not had a hysterectomy. Note: Postmenopausal will be defined in this study as women over the age of 55 who have not had a menstrual period in at least 1 year.
• The effects of E7 TCR T cells on the developing human fetus are unknown. For this reason and because the chemotherapy agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (e.g., intrauterine device, hormonal or barrier method of birth control; abstinence; tubal ligation or vasectomy) prior to study entry and for four months after treatment. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
• Seronegative for HIV (human immunodeficiency virus) antibody. The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment.
• Seronegative for hepatitis B antigen and hepatitis C antibody. If hepatitis C antibody test is positive, then the participant must be tested for the presence of antigen by Reverse transcription polymerase chain reaction (RT-PCR) and be hepatitis C Virus (HCV) ribonucleic acid (RNA) negative.
• Must be willing to participate in Gene Therapy Long Term Follow up Protocol (20C0051), which will follow participants for up to 15 years per Food and Drug Administration (FDA) requirements.
• Participants must have organ and marrow function as defined below:
• leukocytes \>=3,000/mcL
• absolute neutrophil count \>=1,500/mcL

You may not qualify if:

• Previous treatment for invasive cervical cancer including:
• Chemotherapy or other systemic treatments
• Radiation therapy
• Hysterectomy (prior LEEP procedure or cone biopsy is allowed)
• Participants who are receiving any other investigational agents.
• History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations at the time of treatment that would limit compliance with study requirements.
• Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with E7 TCR T cells, breastfeeding should be discontinued if the mother is treated with E7 TCR T cells. These potential risks may also apply to other agents used in this study.
• Participants with any form of systemic immunodeficiency, including acquired deficiency such as HIV or primary immunodeficiency such as Severe Combined Immunodeficiency Disease, are ineligible. The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who have decreased immune competence may be less responsive to the treatment.
• Participants on immunosuppressive drugs including corticosteroids.
• Participants with a second invasive malignancy requiring treatment within the last 2 years are not eligible with the following exceptions:
• Ductal carcinoma in situ (DCIS) of the breast
• Cutaneous skin cancers requiring only local excision

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Results Point of Contact

• Title: Scott M. Norberg D.O.
• Organization: National Cancer Institute

scott.norberg@nih.gov

301-275-9668

Study Officials

• Scott M Norberg, D.O.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: July 20, 2020
• Study Start: January 14, 2021
• Primary Completion: September 15, 2021
• Study Completion: September 15, 2021
• Last Updated: December 15, 2021
• Results First Posted: December 8, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)