Bladder CancerPhase 1/2STAR-EVNCT06394570
Enfortumab Vedotin and Stereotactic Radiation for Localized Bladder Cancer
A Phase 1/2 study testing Enfortumab vedotin in people with Bladder Cancer, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
STAR-EV will evaluate the combination of enfortumab vedotin plus radiotherapy (RT) as neoadjuvant treatment for bladder cancer prior to radical cystectomy surgery. The study will use "dose escalation" to evaluate the safety and efficacy of study treatment at three dose regimens: Level 0: EV treatment followed by RT to… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer
- What is being tested?
- Enfortumab vedotin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Sep 2024to 30 Sep 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- Urothelial carcinoma of the urinary bladder stage cT1-4a (AJCC 8th edition) N0M0 planned for radical cystectomy.
- For cR1 staged patients. the patient must have high grade disease AND be appropriate for cystectomy.
- Mixed cell types with variant histologies (including squamous, plasmacytoid, adenocarcinoma, sarcomatoid, micropapillary, nested, and lipid cell variants) are allowed as long as any urothelial histology is present (i.e. -not 100% variant histology). Small cell/neuroendocrine component is excluded.
- Age >=18.
- Performance status Eastern Cooperative Oncology Group (ECOG) 0-1
- Adequate organ and marrow function as defined below:
Show all 20Show fewer
- •Hematologic:
- -Absolute neutrophil count (ANC) >=1500/mm3
- Platelet count >=100x109/L
- Hemoglobin ≥ 9 g/dL
- •Hepatic:
- Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert's disease
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN
- •Renal:
- No end stage renal disease requiring dialysis allowed
- All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 3 months following completion of study neoadjuvant therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- 7a. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
- 8. Ability to understand and the willingness to sign a written informed consent.
Who cannot join
- No prior systemic therapy (except prior therapy for non-muscle invasive bladder cancer >12 prior to registration) for bladder cancer or prior pelvic radiotherapy. Prior intra-vesical therapies are allowed, including Bacillus Calmette-Guerin (BCG) for non-muscle invasive bladder cancer. Prior chemotherapy for other cancers is allowed if given >=1 year prior to study registration.
- Baseline >= Grade 2 sensory or motor neuropathy
- Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to enfortumab vedotin or other 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 that, in the opinion of the investigator, would limit compliance with study requirements.
- Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UT Southwestern Medical Center
Dallas, Texas, 75390
Amy Rowell, 214-645-9688, amy.rowell@utsouthwestern.edu
Tian Zhang, MD
About this study
Official title: Stereotactic Treatment With neoAdjuvant Radiotherapy and Enfortumab Vedotin: a Phase I/II Study With Safety Lead-In for Localized Bladder Cancer (STAR-EV)
STAR-EV will evaluate the combination of enfortumab vedotin plus radiotherapy (RT) as neoadjuvant treatment for bladder cancer prior to radical cystectomy surgery. The study will use "dose escalation" to evaluate the safety and efficacy of study treatment at three dose regimens:
Level 0: EV treatment followed by RT to the bladder Level 1: EV treatment with RT starting on Cycle 2, Day 15 Level 2: EV treatment with RT starting on Cycle 1, Day 15
Following completion of EV+RT neoadjuvant therapy, all subjects will undergo surgery as part of routine care.
Read the detailed description
STAR EV is a phase I/II trial with safety lead in, designed to assess safety and preliminary efficacy signal in improving pathologic complete response by adding stereotactic radiation to neoadjuvant enfortumab vedotin. Participants will be adult patients with urothelial predominant bladder cancer planned for radical cystectomy.
All participants will undergo the same treatment:
- Enfortumab vedotin (PADCEV) 1.25mg/kg (max 125mg) IV Day 1, 8 q21 day cycle x 3 cycles
- Radiation: Stereotactic radiotherapy to bladder (partial bladder volume preferred) 5 fractions; either sequential to EV treatment or concurrent with EV treatment
- Surgery: Standard of care radical cystectomy and pelvic lymph node dissection with urinary diversion per surgeon discretion.
The study will use a patient safety lead-in incorporating escalation of EV-RT from sequential to concurrent use with pre-defined stopping rules according to treatment-related adverse event (TRAE) rate of grade 3 or above. Primary endpoints are related to safety (maximum tolerated dose "regimen" based on dose limiting toxicities (DLTs) observed) and pathologic complete response rate at the time of surgery. Subjects will be followed for one year following cystectomy, or completion of neoadjuvant therapy for any subject who does not undergo cystectomy for any reason.
- Conditions
- Bladder Cancer
- Being tested
- Enfortumab vedotin
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enfortumab vedotinDrug
Also called PADCEV
Enfortumab Vedotin administered 1.25mg/kg (max 125mg) IV on Day 1 and Day 8 of each 21 day cycle x 3 cycles
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 0 | Experimental | Neoadjuvant therapy of Enfortumab Vedotin 1.25 mg/kg (3 cycles) and sequential Radiation Therapy starting on Cycle 3 Day 21 of EV treatment (32.5 Gray in 5 fractions) Receives: Drug: Enfortumab vedotin |
| Dose Level 1 | Experimental | Neoadjuvant therapy of Enfortumab Vedotin 1.25 mg/kg (3 cycles) and concurrent Radiation Therapy starting on Cycle 2 Day 15 of EV treatment (32.5 Gray in 5 fractions) Receives: Drug: Enfortumab vedotin |
| Dose Level 2 | Experimental | Neoadjuvant therapy of Enfortumab Vedotin 1.25 mg/kg (3 cycles) and concurrent Radiation Therapy starting on Cycle 1 Day 15 of EV treatment (32.5 Gray in 5 fractions) Receives: Drug: Enfortumab vedotin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) Regimen
A standard 3 + 3 dose escalation schedule will be used for all escalations. Enfortumab Vedotin will be given for three 21 day cycles. Radiation therapy will be administered at dose level 0, level 1 or level 2.
Measured: From initiation of Enfortuman Vedotin treatment until post neoadjuvant therapy visit (approximately 120 days)
Pathologic Complete response rate at radical cystectomy
Rate of complete pathologic response in bladder tumor biopsy at cystectomy according to postsurgical staging.
Measured: At radical cystectomy following completion of neoadjuvant therapy (approximately 6 weeks after completion of EV treatment)
Secondary outcomes (2)
Adverse Events
Adverse events reported and observed according to CTCAE v5.0
Measured: From initiation of neoadjuvant therapy to completion of final post treatment study visit (approximately 4 months)
Rate of pathologic downstaging in the bladder
Rate of post surgical pathologic staging being less than clinical staging.
Measured: At radical cystectomy following completion of neoadjuvant therapy (approximately 6 weeks after completion of EV treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2024
- Study start10 Sep 2024
- Primary completion30 Sep 2028 (estimated)
- Study completion30 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Safety lead-in which will assess safety of study therapy in a rule-based "escalation" approach, using the classic "3+3" design.
- Masking
- None (open label)
- Enrolment
- 19 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma Inc
- Responsible party
- Principal investigator, Tian Zhang, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06394570
- Sponsor's protocol ID
- STU-2024-0374
- Acronym
- STAR-EV
- Status last verified
- Sep 2026
- First submitted
- 27 Apr 2024
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stereotactic Treatment With neoAdjuvant Radiotherapy and Enfortumab Vedotin: a Phase I/II Study With Safety Lead-In for Localized Bladder Cancer (STAR-EV)
- ClinicalTrials.gov ID
- NCT06394570
- Acronym / sponsor ID
- STAR-EV / STU-2024-0374
- Conditions
- Bladder Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 19 participants (estimated)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- Astellas Pharma Inc
- Study start
- 10 Sep 2024 (actual)
- Primary completion
- 30 Sep 2028 (estimated)
- Study completion
- 30 Sep 2029 (estimated)
- First posted
- 1 May 2024 (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.
STAR-EV will evaluate the combination of enfortumab vedotin plus radiotherapy (RT) as neoadjuvant treatment for bladder cancer prior to radical cystectomy surgery. The study will use "dose escalation" to evaluate the safety and efficacy of study treatment at three dose regimens:
Level 0: EV treatment followed by RT to the bladder Level 1: EV treatment with RT starting on Cycle 2, Day 15 Level 2: EV treatment with RT starting on Cycle 1, Day 15
Following completion of EV+RT neoadjuvant therapy, all subjects will undergo surgery as part of routine care.
Detailed description
STAR EV is a phase I/II trial with safety lead in, designed to assess safety and preliminary efficacy signal in improving pathologic complete response by adding stereotactic radiation to neoadjuvant enfortumab vedotin. Participants will be adult patients with urothelial predominant bladder cancer planned for radical cystectomy.
All participants will undergo the same treatment:
- Enfortumab vedotin (PADCEV) 1.25mg/kg (max 125mg) IV Day 1, 8 q21 day cycle x 3 cycles
- Radiation: Stereotactic radiotherapy to bladder (partial bladder volume preferred) 5 fractions; either sequential to EV treatment or concurrent with EV treatment
- Surgery: Standard of care radical cystectomy and pelvic lymph node dissection with urinary diversion per surgeon discretion.
The study will use a patient safety lead-in incorporating escalation of EV-RT from sequential to concurrent use with pre-defined stopping rules according to treatment-related adverse event (TRAE) rate of grade 3 or above. Primary endpoints are related to safety (maximum tolerated dose "regimen" based on dose limiting toxicities (DLTs) observed) and pathologic complete response rate at the time of surgery. Subjects will be followed for one year following cystectomy, or completion of neoadjuvant therapy for any subject who does not undergo cystectomy for any reason.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Safety lead-in which will assess safety of study therapy in a rule-based "escalation" approach, using the classic "3+3" design.
| Arm | Type | Receives |
|---|---|---|
| Dose Level 0 | Experimental | Drug: Enfortumab vedotinNeoadjuvant therapy of Enfortumab Vedotin 1.25 mg/kg (3 cycles) and sequential Radiation Therapy starting on Cycle 3 Day 21 of EV treatment (32.5 Gray in 5 fractions) |
| Dose Level 1 | Experimental | Drug: Enfortumab vedotinNeoadjuvant therapy of Enfortumab Vedotin 1.25 mg/kg (3 cycles) and concurrent Radiation Therapy starting on Cycle 2 Day 15 of EV treatment (32.5 Gray in 5 fractions) |
| Dose Level 2 | Experimental | Drug: Enfortumab vedotinNeoadjuvant therapy of Enfortumab Vedotin 1.25 mg/kg (3 cycles) and concurrent Radiation Therapy starting on Cycle 1 Day 15 of EV treatment (32.5 Gray in 5 fractions) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Urothelial carcinoma of the urinary bladder stage cT1-4a (AJCC 8th edition) N0M0 planned for radical cystectomy.
- For cR1 staged patients. the patient must have high grade disease AND be appropriate for cystectomy.
- Mixed cell types with variant histologies (including squamous, plasmacytoid, adenocarcinoma, sarcomatoid, micropapillary, nested, and lipid cell variants) are allowed as long as any urothelial histology is present (i.e. -not 100% variant histology). Small cell/neuroendocrine component is excluded.
- Age >=18.
- Performance status Eastern Cooperative Oncology Group (ECOG) 0-1
Key exclusion criteria (6 listed)
- No prior systemic therapy (except prior therapy for non-muscle invasive bladder cancer >12 prior to registration) for bladder cancer or prior pelvic radiotherapy. Prior intra-vesical therapies are allowed, including Bacillus Calmette-Guerin (BCG) for non-muscle invasive bladder cancer. Prior chemotherapy for other cancers is allowed if given >=1 year prior to study registration.
- Baseline >= Grade 2 sensory or motor neuropathy
- Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to enfortumab vedotin or other 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 that, in the opinion of the investigator, would limit compliance with study requirements.
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 |
|---|---|---|
| Enfortumab vedotinAlso: PADCEVEnfortumab Vedotin administered 1.25mg/kg (max 125mg) IV on Day 1 and Day 8 of each 21 day cycle x 3 cycles | Drug | Dose Level 0, Dose Level 1, Dose Level 2 |
Primary outcome
Maximum Tolerated Dose (MTD) Regimen
Time frame: From initiation of Enfortuman Vedotin treatment until post neoadjuvant therapy visit (approximately 120 days)
A standard 3 + 3 dose escalation schedule will be used for all escalations. Enfortumab Vedotin will be given for three 21 day cycles. Radiation therapy will be administered at dose level 0, level 1 or level 2.
Pathologic Complete response rate at radical cystectomy
Time frame: At radical cystectomy following completion of neoadjuvant therapy (approximately 6 weeks after completion of EV treatment)
Rate of complete pathologic response in bladder tumor biopsy at cystectomy according to postsurgical staging.
2 secondary outcomes
Adverse Events
Time frame: From initiation of neoadjuvant therapy to completion of final post treatment study visit (approximately 4 months)
Rate of pathologic downstaging in the bladder
Time frame: At radical cystectomy following completion of neoadjuvant therapy (approximately 6 weeks after completion of EV treatment)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2026.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Enfortumab vedotin in people with Bladder Cancer, run by University of Texas Southwestern Medical Center 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 20 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 30 Sep 2026. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tian Zhang, MD, MHS (214-648-4180, tian.zhang@utsouthwestern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) Regimen (time frame: From initiation of Enfortuman Vedotin treatment until post neoadjuvant therapy visit (approximately 120 days)). 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 30 Sep 2026.