Uterine Cervical NeoplasmsEarly Phase 1NCT04476251
E7 TCR T Cell Induction Immunotherapy for Stage IIB-IVA Cervical Cancer
A Early Phase 1 study testing E7 T-Cell Receptor (TCR) in people with Uterine Cervical Neoplasms, run by National Cancer Institute (NCI) at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Uterine Cervical Neoplasms
- What is being tested?
- E7 T-Cell Receptor (TCR)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jan 2021to 15 Sep 2021
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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.
Show all 14Show fewer
- 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 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.
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Pilot Study of E7 TCR T Cell Induction Immunotherapy for Stage IIB-IVA Cervical Cancer
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.
Read more
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....
Read the 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.
- Conditions
- Uterine Cervical Neoplasms
- Being tested
- E7 T-Cell Receptor (TCR)
- Keywords
- T Cell Receptor, Immunotherapy, Aldesleukin, Cyclophosphamide, Fludarabine
- Medical subject headings
- Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
E7 T-Cell Receptor (TCR)Biological
Patients will receive up to 3x10^10 E7 T-Cell Receptor (TCR) T cells (i.e. TCR+ cells).
| Study group | Role | What they receive |
|---|---|---|
| Arm 1/E7 T-Cell Receptor (TCR) T Cell Therapy | Experimental | E7 TCR T Cell Therapy Receives: Biological: E7 T-Cell Receptor (TCR) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 months
Secondary outcomes (4)
Fraction of Participants With Relapse-free Survival at 2 Years and 5 Years Following Definitive Standard of Care Therapy
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.
Measured: 2 yrs and 5 yrs
Fraction of Participants With Grade 1-5 Adverse Events
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.
Measured: 1 year
Percentage of E7 T-Cell Receptor (TCR)T Cells Following Completion of Chemoradiation
Percentage of E7 T-Cell Receptor (TCR)T cells following completion of chemoradiation
Measured: 1 year
Fraction of Participants Who Achieve an Objective Response (Partial Response + Complete Response) Following E7 T-Cell Receptor (TCR) T Cell Induction Therapy
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2020
- Study start14 Jan 2021
- Primary completion15 Sep 2021
- Study completion15 Sep 2021
Why it stopped: Multiple logistical challenges
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Uterine Cervical NeoplasmsStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Scott Norberg, D.O., National Cancer Institute (NCI)
- Investigators
- Scott M Norberg, D.O., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04476251
- Sponsor's protocol ID
- 200116
- Other IDs
- 20-C-0116
- Status last verified
- Dec 2021
- First submitted
- 16 Jul 2020
- Last updated
- 15 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of E7 TCR T Cell Induction Immunotherapy for Stage IIB-IVA Cervical Cancer
- ClinicalTrials.gov ID
- NCT04476251
- Acronym / sponsor ID
- 200116
- Conditions
- Uterine Cervical Neoplasms
- Keywords
- T Cell Receptor, Immunotherapy, Aldesleukin, Cyclophosphamide, Fludarabine
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Multiple logistical challenges
- Enrolment
- 1 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 14 Jan 2021 (actual)
- Primary completion
- 15 Sep 2021 (actual)
- Study completion
- 15 Sep 2021 (actual)
- First posted
- 20 Jul 2020 (actual)
- Results
- Posted 8 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1/E7 T-Cell Receptor (TCR) T Cell Therapy | Experimental | Biological: E7 T-Cell Receptor (TCR)E7 TCR T Cell Therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (14 listed)
- Previous treatment for invasive cervical cancer including:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| E7 T-Cell Receptor (TCR)Patients will receive up to 3x10^10 E7 T-Cell Receptor (TCR) T cells (i.e. TCR+ cells). | Biological | Arm 1/E7 T-Cell Receptor (TCR) T Cell Therapy |
Primary outcome
The Fraction of Participants for Whom E7 T-Cell Receptor (TCR) Induction Therapy is Feasible in Participants With Cervical Cancer
Time frame: 6 months
The Fraction of participants for whom E7 T-Cell Receptor (TCR) induction therapy is feasible in participants with cervical cancer
4 secondary outcomes
Fraction of Participants With Relapse-free Survival at 2 Years and 5 Years Following Definitive Standard of Care Therapy
Time frame: 2 yrs and 5 yrs
Fraction of Participants With Grade 1-5 Adverse Events
Time frame: 1 year
Percentage of E7 T-Cell Receptor (TCR)T Cells Following Completion of Chemoradiation
Time frame: 1 year
Fraction of Participants Who Achieve an Objective Response (Partial Response + Complete Response) Following E7 T-Cell Receptor (TCR) T Cell Induction Therapy
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott M Norberg, D.O. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing E7 T-Cell Receptor (TCR) in people with Uterine Cervical Neoplasms, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Fraction of Participants for Whom E7 T-Cell Receptor (TCR) Induction Therapy is Feasible in Participants With Cervical Cancer (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2021.