Metastatic Urothelial CarcinomaPhase 2NCT04383067
A Phase 2, Single-Center, Open Label Study of Autologous, Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Urothelial Carcinoma Patients
A Phase 2 study testing Tumor Infiltrating Lymphocytes (TIL) and Proleukin in people with Metastatic Urothelial Carcinoma, run by Sheba Medical Center at 1 site in Israel.
Trial summary
An autologous, Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Urothelial Carcinoma Patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Urothelial Carcinoma
- What is being tested?
- Tumor Infiltrating Lymphocytes (TIL) and Proleukin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteIsrael
- Study dates
- 12 May 2020to 1 Jun 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed Urothelial Carcinoma
- Progressed on first line platinum-based chemotherapy and on second line immunotherapy or targeted therapy (FGFR inhibitor)
- Measurable metastatic Urothelial Carcinoma with at least one lesion that is resectable for TIL generation.
- Patients with one or more brain metastases less than 1 cm each, and any patients with 1 or 2 brain metastases greater than 1 cm must have been treated and stable for 4 weeks.
- Greater than or equal to 18 years of age.
- Willing to practice birth control from the start of chemotherapy until 120 days after release from the hospital.
Show all 24Show fewer
- Life expectancy of greater than three months
- Willing to sign a durable power of attorney
- Able to understand and sign the Informed Consent Document
- Clinical performance status of ECOG 0 or 1
- Hematology:
- Absolute neutrophil count greater than 1000/mm3 without support of filgrastim
- Normal WBC ( > 3000/mm3).
- Hemoglobin greater than 8.0 g/dL
- Platelet count greater than 100,000/mm3
- Serology:
- Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus can be less responsive to the experimental treatment and more susceptible to its toxicities.)
- Seronegative for Hepatitis B or Hepatitis C. (patients who recovered from previous infection and have no detected HBSAg or HCV RNA are allowed).
- Chemistry:
- Serum ALT/AST less than three times the upper limit of normal (ULN).
- Serum creatinine less than or equal to 1.6 mg/dL
- Total bilirubin no more than x1.5 times the ULN, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dL.
- Negative pregnancy test in women of child bearing potential because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
- More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo). Patients may have undergone minor surgical procedures with the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.
Who cannot join
- Upper tract Urothelial Carcinoma
- History of nephrectomy
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the non-myeloablative, lymphodepleting induction regimen on the fetus or infant.
- Systemic steroid therapy required (patients that require replacement therapy for adrenal insufficiency may be enrolled if steroid treatment dose do not exceed 10 mg of prednisone or equivalent).
- Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
Show all 12Show fewer
- Opportunistic infections (the experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
- History of severe immediate hypersensitivity reaction to any of the agents used in this study, including history of an anaphylactic reaction to penicillin or gentamicin
- History of coronary revascularization or ischemic heart disease.
- Any patient known to have an LVEF less than or equal to 50%.
- Documented LVEF of less than or equal to 50% tested in patients with clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second- or third-degree heart block
- Documented FEV1 and DLCO (relative to predicted) less than or equal to 60%
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Sheba Medical Center
Ramat Gan, 5262100
Ronnie Shapira, Dr, 972-3-5308414, ronnie.shapira@sheba.health.gov.il
Meital Bar, 972-3-5305201, meital.bar@sheba.healtnh.gov.il
About this study
An autologous, Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Urothelial Carcinoma Patients.
Read the detailed description
This is a phase II single-center study of Tumor Infiltrating Lymphocytes (TIL) in urothelial carcinoma patients who failed at least one line of platinum based chemotherapy and one line of immunotherapy of targeted therapy.
Patients will undergo a baseline evaluation including imaging, blood and urine samples, EVG and physical examination to confirm suitability for the study.
Eligible patients will undergo surgery to collect a tumor sample for TIL culturing.
Patients will receive an autologus TIL infusion once the cells have been properly cultured.
Following the infusion, patients will receive a high dose of IL-2.
Following the intervention, patients will be monitored to evaluate study endpoints.
- Conditions
- Metastatic Urothelial Carcinoma
- Being tested
- Tumor Infiltrating Lymphocytes (TIL), Proleukin
- Keywords
- Urothelial cancer, Tumor infiltrating lymphocytes, Cellular therapy
- Medical subject headings
- Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tumor Infiltrating Lymphocytes (TIL)Procedure or surgery
Patient with metastatic urothelial carcinoma will undergo a autologous lymphocyte transplantation. Patient will undergo surgery to remove either the primary tumor or a tumor metastasis. The cells collected in this surgey will be cultured and reintroduced to the patient. Following the cell infusion, patient will receive a high-dose bolus of IL-2.
ProleukinDrug
high-dose (720,000 IU/kg) IL-2 will be administered every 8 hours, to tolerance. A maximum of 10 doses will be administered
| Study group | Role | What they receive |
|---|---|---|
| Tumor Infiltrating Lymphocytes (TIL) | Experimental | Not described Receives: Procedure: Tumor Infiltrating Lymphocytes (TIL); Drug: Proleukin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy endpoint Objective Tumor response according to RECICT 1.1
The primary efficacy endpoint is defined as at least a 20% clinical benefit expressed as the sum of CR+PR+SD (each of these parameters defined as persisting for at least for 12 weeks).
Measured: 3 Years
Safety endpoint Assess Adverse Events using CTCAE V4.03 during treatment and FU
The primary safety endpoint of the study is to evaluate the overall toxicity profile of the ACT procedure, with an emphasis on the side effects of the reduced intensity, non-myeloablative, lymphodepleting induction regimen.
Measured: 3 Years
Secondary outcomes (3)
Overall Survival
Overall Survival (OS) according to RECICT 1.1
Measured: 3 Years
Progression-Free Survival
Progression-Free Survival (PFS) according to RECICT 1.1
Measured: 3 Years
Quality of Life (QoL) Assessment
Assessment of QoL using disease specific modules of the EORTC QLQ-C30 (version 3.0)
Measured: 3 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2020
- Study start12 May 2020
- Primary completion1 Jun 2022 (estimated)
- Study completion1 Jun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by Sheba Medical CenterThe 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Dr. Ronnie Shapira, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04383067
- Sponsor's protocol ID
- SHEBA-19-6407-RS-TIL TCC
- Status last verified
- May 2020
- First submitted
- 3 May 2020
- Last updated
- 11 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Single-Center, Open Label Study of Autologous, Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Urothelial Carcinoma Patients
- ClinicalTrials.gov ID
- NCT04383067
- Acronym / sponsor ID
- SHEBA-19-6407-RS-TIL TCC
- Conditions
- Metastatic Urothelial Carcinoma
- Keywords
- Urothelial cancer, Tumor infiltrating lymphocytes, Cellular therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Sheba Medical CenterOther government
- Study start
- 12 May 2020 (actual)
- Primary completion
- 1 Jun 2022 (estimated)
- Study completion
- 1 Jun 2023 (estimated)
- First posted
- 11 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An autologous, Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Urothelial Carcinoma Patients.
Detailed description
This is a phase II single-center study of Tumor Infiltrating Lymphocytes (TIL) in urothelial carcinoma patients who failed at least one line of platinum based chemotherapy and one line of immunotherapy of targeted therapy.
Patients will undergo a baseline evaluation including imaging, blood and urine samples, EVG and physical examination to confirm suitability for the study.
Eligible patients will undergo surgery to collect a tumor sample for TIL culturing.
Patients will receive an autologus TIL infusion once the cells have been properly cultured.
Following the infusion, patients will receive a high dose of IL-2.
Following the intervention, patients will be monitored to evaluate study endpoints.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tumor Infiltrating Lymphocytes (TIL) | Experimental | Procedure: Tumor Infiltrating Lymphocytes (TIL), Drug: Proleukin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Histologically confirmed Urothelial Carcinoma
- Progressed on first line platinum-based chemotherapy and on second line immunotherapy or targeted therapy (FGFR inhibitor)
- Measurable metastatic Urothelial Carcinoma with at least one lesion that is resectable for TIL generation.
- Patients with one or more brain metastases less than 1 cm each, and any patients with 1 or 2 brain metastases greater than 1 cm must have been treated and stable for 4 weeks.
- Greater than or equal to 18 years of age.
Key exclusion criteria (12 listed)
- Upper tract Urothelial Carcinoma
- History of nephrectomy
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the non-myeloablative, lymphodepleting induction regimen on the fetus or infant.
- Systemic steroid therapy required (patients that require replacement therapy for adrenal insufficiency may be enrolled if steroid treatment dose do not exceed 10 mg of prednisone or equivalent).
- Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
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 |
|---|---|---|
| Tumor Infiltrating Lymphocytes (TIL)Patient with metastatic urothelial carcinoma will undergo a autologous lymphocyte transplantation. Patient will undergo surgery to remove either the primary tumor or a tumor metastasis. The cells collected in this surgey will be cultured and reintroduced to the patient. Following the cell infusion, patient will receive a high-dose bolus of IL-2. | Procedure or surgery | Tumor Infiltrating Lymphocytes (TIL) |
| Proleukinhigh-dose (720,000 IU/kg) IL-2 will be administered every 8 hours, to tolerance. A maximum of 10 doses will be administered | Drug | Tumor Infiltrating Lymphocytes (TIL) |
Primary outcome
Efficacy endpoint Objective Tumor response according to RECICT 1.1
Time frame: 3 Years
The primary efficacy endpoint is defined as at least a 20% clinical benefit expressed as the sum of CR+PR+SD (each of these parameters defined as persisting for at least for 12 weeks).
Safety endpoint Assess Adverse Events using CTCAE V4.03 during treatment and FU
Time frame: 3 Years
The primary safety endpoint of the study is to evaluate the overall toxicity profile of the ACT procedure, with an emphasis on the side effects of the reduced intensity, non-myeloablative, lymphodepleting induction regimen.
3 secondary outcomes
Overall Survival
Time frame: 3 Years
Progression-Free Survival
Time frame: 3 Years
Quality of Life (QoL) Assessment
Time frame: 3 Years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2021.
Related trials for Metastatic Urothelial Carcinoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
RecruitingPhase 3
A Study Comparing the Combination of Pembrolizumab and Sacituzumab Govitecan-hziy Versus Standard of Care in the Treatment of Advanced Urothelial Cancer
Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma
RecruitingPhase 2
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
Bladder Adenocarcinoma, Bladder Clear Cell Adenocarcinoma
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tumor Infiltrating Lymphocytes (TIL) and Proleukin in people with Metastatic Urothelial Carcinoma, run by Sheba Medical Center at 1 site in Israel.
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 24 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 11 Feb 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 Israel. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ronnie Shapira, MD. (+972-3-5308414, Ronnie.Shapira@sheba.health.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy endpoint Objective Tumor response according to RECICT 1.1 (time frame: 3 Years). The study lists 2 primary outcomes in all. 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 11 Feb 2021.