Trial Title:
A Study of Enfortumab Vedotin in People with Urothelial Carcinoma of the Upper Urinary Tract
NCT ID:
NCT05868265
Condition:
Urothelial Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Transitional Cell
Conditions: Keywords:
Enfortumab Vedotin
Upper Urinary Tract
High Grade
Radical surgery + pelvic lymph node dissection
21-393
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
This is a single arm phase II trial.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Enfortumab Vedotin
Description:
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.
Arm group label:
Enfortumab Vedotin
Intervention type:
Procedure
Intervention name:
Radical surgery
Description:
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).
Arm group label:
Enfortumab Vedotin
Summary:
The purpose of this study is to find out whether the study drug, enfortumab vedotin, is
an effective and safe treatment for people who have urothelial carcinoma of the upper
urinary tract. Study participants will be people who are not eligible to receive or have
chosen not to receive the chemotherapy drug cisplatin for treatment of their cancer. In
addition, all participants will be planning on having standard surgery to remove their
tumor.
Criteria for eligibility:
Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Address:
City:
Basking Ridge
Zip:
07920
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gopakumar Iyer, MD
Phone:
646-888-4717
Facility:
Name:
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Address:
City:
Middletown
Zip:
07748
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gopakumar Iyer, MD
Phone:
646-888-4717
Facility:
Name:
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Address:
City:
Montvale
Zip:
07645
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gopakumar Iyer, MD
Phone:
646-888-4717
Facility:
Name:
Memorial Sloan Kettering Suffolk - Commack (Limited protocol activities)
Address:
City:
Commack
Zip:
11725
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gopakumar Iyer, MD
Phone:
646-888-4717
Facility:
Name:
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gopakumar Iyer, MD
Phone:
646-888-4717
Contact backup:
Last name:
Jonathan Rosenberg, MD
Phone:
646-888-4741
Facility:
Name:
Memorial Sloan Kettering Nassau (Limited protocol activities)
Address:
City:
Uniondale
Zip:
11553
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gopakumar Iyer, MD
Phone:
646-888-4717
Facility:
Name:
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Address:
City:
West Harrison
Zip:
10604
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gopakumar Iyer, MD
Phone:
646-888-4717
Start date:
June 2, 2023
Completion date:
May 2025
Lead sponsor:
Agency:
Memorial Sloan Kettering Cancer Center
Agency class:
Other
Collaborator:
Agency:
Astellas Pharma US, Inc.
Agency class:
Industry
Source:
Memorial Sloan Kettering Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05868265
http://www.mskcc.org/mskcc/html/44.cfm
