Description:
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 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 heart s 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 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....
Title
- Brief Title: E7 TCR T Cell Induction Immunotherapy for Stage IIB-IVA Cervical Cancer
- Official Title: A Pilot Study of E7 TCR T Cell Induction Immunotherapy for Stage IIB-IVA Cervical Cancer
Clinical Trial IDs
- ORG STUDY ID:
200116
- SECONDARY ID:
20-C-0116
- NCT ID:
NCT04476251
Conditions
- Uterine Cervical Neoplasms
Interventions
Drug | Synonyms | Arms |
---|
E7 TCR | | Arm 1 |
Purpose
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 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 heart s 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 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 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 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 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 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.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm 1 | Experimental | E7 TCR T Cell Therapy | |
Eligibility Criteria
-INCLUSION CRITERIA:
1. 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 stage IIIC-IVA (2018 International FIGO Staging
System)
- After lead-in safety cohort: FIGO stage IIB-IVA (2018 International FIGO Staging
System)
2. HPV16+ tumor and HLA-A*02:01+ HLA type. Note: HLA-A*02 is also acceptable for
enrollment but not for treatment.
3. Measurable disease by RECIST 1.1 criteria or PERCIST (if not eligible by RECIST 1.1).
4. 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.
5. ECOG performance status 0 or 1.
6. 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.
7. 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.
8. Seronegative for HIV 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.
9. 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
RT-PCR and be HCV RNA negative.
10. 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.
11. Participants must have organ and marrow function as defined below:
- leukocytes >=3,000/mcL
- absolute neutrophil count >=1,500/mcL
- platelets >=100,000/mcL
- hemoglobin >=9.0 g/dL
- total bilirubin within normal institutional limits except in participants with
Gilbert s Syndrome who must have a total bilirubin < 3.0 mg/dL
- AST(SGOT)/ALT(SGPT) Serum ALT/AST < 2.5X ULN
- creatinine clearance Calculated creatinine clearance (CrCl) >=50 mL/min/1.73 m^2
for participants with creatinine levels above institutional normal (by the
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation)
12. Ability of subject to understand and the willingness to sign a written informed
consent document.
EXCLUSION CRITERIA:
1. Previous treatment for invasive cervical cancer including:
- Chemotherapy or other systemic treatments
- Radiation therapy
- Hysterectomy (prior LEEP procedure or cone biopsy is allowed)
2. Participants who are receiving any other investigational agents.
3. History of severe allergic reactions attributed to compounds of similar chemical or
biologic composition to agents used in study.
4. 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.
5. 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.
6. 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.
7. Participants on immunosuppressive drugs including corticosteroids.
8. Participants with autoimmune diseases such as Crohn s disease, ulcerative colitis,
rheumatoid arthritis, autoimmune hepatitis, autoimmune pancreatitis, or systemic lupus
erythematosus. Hypothyroidism, vitiligo and other minor autoimmune disorders are not
exclusionary.
9. 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | determine if it is feasible to administer E7 TCR T cells prior to definitive therapy in patients with cervical cancer. |
Time Frame: | 6 months |
Safety Issue: | |
Description: | the fraction of subjects for whom E7 TCR induction therapy is feasible |
Secondary Outcome Measures
Measure: | to assess the relapse-free survival at 2 years and 5 years following definitive standard of care therapy |
Time Frame: | 2 yrs and 5 yrs |
Safety Issue: | |
Description: | fraction who achieve a success will be determined and reported |
Measure: | to evaluate the safety of E7 induction therapy |
Time Frame: | 1 year |
Safety Issue: | |
Description: | the types and grades of toxicity obtained will be report and findings described. fraction who achieve a success will be determined and reported |
Measure: | to determine the percentage of E7 TCR T cells following completion of chemoradiation |
Time Frame: | 1 year |
Safety Issue: | |
Description: | the types and grades of toxicity obtained will be report and findings described. fraction who achieve a success will be determined and reported |
Measure: | to assess objective response rate following E7 induction therapy |
Time Frame: | 1 year |
Safety Issue: | |
Description: | fraction who achieve a success will be determined and reported |
Details
Phase: | Early Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Suspended |
Lead Sponsor: | National Cancer Institute (NCI) |
Trial Keywords
- T Cell Receptor
- Immunotherapy
- Aldesleukin
- Cyclophosphamide
- Fludarabine
Last Updated
February 17, 2021