- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05868265
A Study of Enfortumab Vedotin in People With Urothelial Carcinoma of the Upper Urinary Tract
Neoadjuvant Enfortumab Vedotin in High-Grade Urothelial Carcinoma of the Upper Urinary Tract (Including Ureter and Renal Pelvis)
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Min Yuen Teo, MD
- Phone Number: 646-888-4867
- Email: teom@mskcc.org
Study Contact Backup
- Name: Jonathan Rosenberg, MD
- Phone Number: 646-422-4461
Study Locations
-
-
New Jersey
-
Basking Ridge, New Jersey, United States, 07920
- Recruiting
- Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
-
Contact:
- Min Yuen Teo, MD
- Phone Number: 646-888-4867
-
Middletown, New Jersey, United States, 07748
- Recruiting
- Memorial Sloan Kettering Monmouth (Limited protocol activities)
-
Contact:
- Min Yuen Teo, MD
- Phone Number: 646-888-4867
-
Montvale, New Jersey, United States, 07645
- Recruiting
- Memorial Sloan Kettering Bergen (Limited Protocol Activities)
-
Contact:
- Min Yuen Teo, MD
- Phone Number: 646-888-4867
-
-
New York
-
Commack, New York, United States, 11725
- Recruiting
- Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)
-
Contact:
- Min Yuen Teo, MD
- Phone Number: 646-888-4867
-
Harrison, New York, United States, 10604
- Recruiting
- Memorial Sloan Kettering Westchester (Limited Protocol Activities)
-
Contact:
- Min Yuen Teo, MD
- Phone Number: 646-888-4867
-
New York, New York, United States, 10065
- Recruiting
- Memorial Sloan Kettering Cancer Center (All Protocol Activities)
-
Contact:
- Min Yuen Teo, MD
- Phone Number: 646-888-4867
-
Contact:
- Jonathan Rosenberg, MD
- Phone Number: 646-888-4741
-
Uniondale, New York, United States, 11553
- Recruiting
- Memorial Sloan Kettering Nassau (Limited Protocol Activities)
-
Contact:
- Min Yuen Teo, MD
- Phone Number: 646-888-4867
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Histologically confirmed high grade urothelial carcinoma of the upper tract and/or radiographically visible tumor stage T2-T4a N0/x M0 disease with positive selective urinary cytology. Hydronephrosis associated with tumor on imaging or biopsy will be considered invasive by definition. (Variant histology is acceptable if there is a predominant urothelial component. Discussion with PI strongly encouraged.) Retroperitoneal lymph nodes <15 mm in the short axis will be eligible.
Patients who are
o Ineligible for cisplatin based on any of the following criteria:
- Estimated or calculated creatinine clearance ≥ 30ml/min but < 60 ml/min
- Grade 2 or above audiometric hearing loss (per CTCAE v4.0) or
- Declined cisplatin-based neoadjuvant chemotherapy, as documented in medical chart
- Availability of tumor specimen block, cell block or 30 unstained slides from diagnosis. Patients with fewer than 30 slides available may be enrolled after discussion with the Principal Investigator.Additional research biopsy is not required.
- Karnofsky performance status ≥ 70%.
- Medically appropriate candidate for radical surgery (nephroureterectomy, nephrectomy, or ureterectomy), as per MSK Attending Urologic Oncologist
- Age ≥ 18 years.
Required initial laboratory values:
- Absolute neutrophil count ≥ 1.5 x 10^9 /L
- Platelets ≥ 100 x 109 /L
- Bilirubin ≤1.5 times the upper limit of normal (x ULN)
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN PTT/PT ≤1.5 x ULN or INR < 1.7 x ULN for patients who are not receiving therapeutic anticoagulation. Patients receiving therapeutic anticoagulation should be on a stable dose
- If patients are HIV (+) they are eligible as long as they have: cd4 >200, undetectable viral load and on HAART therapy.
Exclusion Criteria:
- Presence of metastatic disease.
- Prior treatment with systemic chemotherapy or radiotherapy for urothelial cancer of the bladder within the last 2 years. (Prior intravesical treatment such as BCG is allowed).
- Grade 2 or higher peripheral neuropathy.
- Patients with active keratitis or corneal ulcerations. Patients with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator.
- Patients with uncontrolled diabetes. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c 7% to <8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
- Unstable angina.
- New York Heart Association (NYHA) Grade II or greater congestive heart failure.
- History of myocardial infarction within 6 months.
- History of stroke within 6 months.
- Evidence of bleeding diathesis or coagulopathy. Therapeutic anticoagulation is permitted, but patients must be on a stable dose.
- Major surgical procedure within 28 days prior to the study. (Transurethral resection of bladder tumor is permitted)
- Serious, non-healing wound, ulcer, or bone fracture.
- Patients with active tuberculosis.
- Other prior malignancy active within the previous 2 years except for local or organ confined early stage cancer that has been definitively treated with curative intent or does not require treatment, does not require ongoing treatment, has no evidence of active disease, and has a negligible risk of recurrence and is therefore unlikely to interfere with the endpoints of the study.
- Prior treatment with enfortumab vedotin or other MMAE-based antibody-drug conjugates (ADCs).
- No known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Women who are breastfeeding or pregnant as evidenced by a positive pregnancy test within 14 days of first dose.
- Known severe (≥ Grade 3) hypersensitivity to enfortumab vedotin or to any excipient contained in the drug formulation of enfortumab vedotin (including histidine, trehalose dihydrate, and polysorbate 20).
- Male subjects who are unwilling to use contraception during the treatment and for at least 31 weeks after the last dose of study treatment (5 half-lives of study drug plus 90 days duration of sperm turnover).
Women of childbearing potential (WOCBP) not using a medically acceptable means of contraception throughout the study treatment and for at least 23 weeks following the last dose of study treatment (5 half-lives of study drug plus 30 days duration of ovulatory cycle).
°WOCBP are defined as those who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Postmenopausal is defined as:
- Amenorrhea ≥ 12 consecutive months without another cause, or
- For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
- Inability to comply with study and/or follow-up procedures.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Enfortumab Vedotin
All patients will receive enfortumab vedotin at 1.25 g/kg on days 1 and 8 of 21 days cycle, for a total of three cycles, followed by radical nephroureterectomy, ureterectomy, or nephrectomy, depending on the site of the tumor and per the clinical decision of the treating urologist.
|
All patients will receive enfortumab vedotin at 1.25 mg/kg on days 1 and 8 of 21 days cycle, for a total of three cycles.
Radical surgery, such as radical nephroureterectomy, nephrectomy or ureterectomy is to take place within 60 days from the last dose of treatment end of cycle 3 (i.e., cycle 3 day 22).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of patients who achieve pathologic complete response
Time Frame: up to 2 years
|
The absence of residual disease on pathologic evaluation on surgical specimen following neoadjuvant enfortumab vedotin for UTUC.
Pathologists will assess surgical specimens systematically using criteria agreed upon for all conventional neoadjuvant treatment based on the AJCC TNM staging system.
|
up to 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The rate of grade 3 - 4 toxicity
Time Frame: up to 2 years
|
according to CTCAE v5.0.
|
up to 2 years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Min Yuen Teo, MD, Memorial Sloan Kettering Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 21-393
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Urothelial Carcinoma
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Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingMetastatic Bladder Urothelial Carcinoma | Metastatic Renal Pelvis Urothelial Carcinoma | Metastatic Ureter Urothelial Carcinoma | Metastatic Urethral Urothelial Carcinoma | Metastatic Urothelial Carcinoma | Locally Advanced Bladder Urothelial Carcinoma | Locally Advanced Renal Pelvis Urothelial... and other conditionsUnited States
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Roswell Park Cancer InstituteIovance Biotherapeutics, Inc.WithdrawnMetastatic Bladder Urothelial Carcinoma | Metastatic Renal Pelvis Urothelial Carcinoma | Metastatic Ureter Urothelial Carcinoma | Metastatic Urethral Urothelial Carcinoma | Unresectable Renal Pelvis Urothelial Carcinoma | Unresectable Ureter Urothelial CarcinomaUnited States
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University of UtahNational Cancer Institute (NCI)RecruitingMetastatic Urothelial Carcinoma | Locally Advanced Urothelial Carcinoma | Unresectable Urothelial Carcinoma | Infiltrating Urothelial Carcinoma, Sarcomatoid VariantUnited States
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National Cancer Institute (NCI)Active, not recruitingMetastatic Urothelial Carcinoma | Stage III Bladder Urothelial Carcinoma AJCC v6 and v7 | Stage IV Bladder Urothelial Carcinoma AJCC v7 | Locally Advanced Urothelial Carcinoma | Recurrent Urothelial Carcinoma | Unresectable Urothelial Carcinoma | Advanced Urothelial CarcinomaUnited States
-
Emory UniversityNational Cancer Institute (NCI); ExelixisRecruitingMetastatic Urothelial Carcinoma | Locally Advanced Urothelial Carcinoma | Unresectable Urothelial Carcinoma | Infiltrating Bladder Urothelial Carcinoma With Squamous DifferentiationUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingMetastatic Urothelial Carcinoma | Infiltrating Bladder Urothelial Carcinoma, Plasmacytoid Variant | Infiltrating Bladder Urothelial Carcinoma Sarcomatoid Variant | Infiltrating Bladder Urothelial Carcinoma With Glandular Differentiation | Infiltrating Bladder Urothelial Carcinoma With Squamous... and other conditionsUnited States
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Mamta ParikhNational Cancer Institute (NCI); Karyopharm Therapeutics IncRecruitingMetastatic Urothelial Carcinoma | Locally Advanced Urothelial Carcinoma | Advanced Urothelial Carcinoma | Refractory Urothelial CarcinomaUnited States
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National Cancer Institute (NCI)Active, not recruitingMetastatic Bladder Urothelial Carcinoma | Metastatic Ureter Urothelial Carcinoma | Stage IV Bladder Urothelial Carcinoma AJCC v7 | Metastatic Renal Pelvis and Ureter Urothelial CarcinomaUnited States
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University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedStage II Bladder Urothelial Carcinoma | Stage III Bladder Urothelial Carcinoma | Stage 0is Bladder Urothelial Carcinoma | Stage I Bladder Urothelial CarcinomaUnited States
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Mayo ClinicNational Cancer Institute (NCI)WithdrawnInfiltrating Bladder Urothelial Carcinoma | Stage II Bladder Urothelial Carcinoma | Stage IV Bladder Urothelial Carcinoma | Stage III Bladder Urothelial CarcinomaUnited States
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