None listed
Conditions
Interventions
Drug : Enfortumab Vedotin (EV) is administered on days 1, 8, and 15 of a 28-day cycle until disease progression, intolerable toxicity, or death occurs. The dose is 1.25 mg/kg (maximum 125 mg). For pat
Sponsors
Asan Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Institutional Review Board (IRB) approved written informed consent must be obtained from the subject prior to any study-related procedures 2) Age 19 or older 3) Histologically confirmed adenocarcinoma of bladder/urachal remnant that is clinically consistent with urachal cancer. ? Origin in the anterior wall or dome of the bladder ? Predominant invasion of muscularis or deeper tissues ? No obvious origin from the overlying urothelium (relative normal-looking urothelial mucosa) ? No primary adenocarcinoma elsewhere 4) Patients with locally advanced, recurrent, or metastatic disease not amenable to surgery, radiotherapy, or combined modality therapy with curative intent 5) Disease progression during or after systemic treatment with 5-FU and platinum-based chemotherapy [for example, 5-FU plus cisplatin (FP) regimen, 5-FU, leucovorin, and oxaliplatin (FOLFOX), or 5-FU, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) ] in the locally advanced/recurrent/metastatic, neoadjuvant or adjuvant setting. If 5-FU and platinum-based chemotherapy was administered in the adjuvant/neoadjuvant setting, subject must have progressed within 6 months of completion. 6) Other systemic treatments in the locally advanced/recurrent/metastatic setting are permitted, except for nectin-4 targeting antibody-drug conjugate. 7) ECOG PS 0-2 (see appendix 1) 8) Measurable disease according to RECIST v1.1 criteria 9) Adequate bone marrow, hepatic, and renal function • Hematology - Neutrophil =1,500/mm3 - Platelet = 100,000/mm3 - Hemoglobin=9 g/dL • Liver function tests - Total bilirubin = 1.5 xULN - AST, ALT = 3 xULN (in case of liver metastasis, 5 x upper limit of normal) • Renal function tests - Creatinine clearance = 30 mL/min 10) Life expectancy more than 3 months 11) Female subject must either: • Be of nonchildbearing potential: - Postmenopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to screening, or - Documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy). Note: Those who are amenorrheic due to an alternative medical cause are not considered postmenopausal and must follow the criteria for childbearing potential subjects. • Or, if of childbearing potential: - Agree not to try to become pregnant during the study and for at least 6 months after the final study drug administration, - And have a negative urine or serum pregnancy test within 7 days prior to Day 1 (Females with false positive results and documented verification of negative pregnancy status are eligible for participation), - And if heterosexually active, agree to consistently use 1 form of highly effective birth control * starting at screening and throughout the study period and for at least 6 months after the final study drug administration. 12) A sexually active male subject with female partner(s) who is of childbearing potential is eligible if: • Agrees to use a male condom starting at screening and continue throughout the study treatment and for 6 months after final study drug administration. If the male subject has not had a vasectomy or is not sterile as defined below, their female partner(s) is utilizing 1 form of highly effective birth control* starting at screening and continue throughout study treatment and for 6 months after the male subject receives his final study drug administration. *Highly effective forms of birth co
Exclusion criteria
Exclusion criteria: 1) Pregnancy or breast feeding 2) Previous radiotherapy to the only measurable lesion: but previous radiotherapy will be permitted unless the lesion is the only measurable lesion 3) Previous treatment with enfortumab vedotin or other antibody-drug conjugate targeting nectin-4 or containing monomethyl auristatin-E 4) Uncontrolled CNS metastasis (brain and/or leptomeningeal metastasis) 5) Grade 2 or more peripheral neuropathy 6) Subject has ongoing clinically significant toxicity (Grade 2 or higher with the exception of alopecia) associated with prior treatment (including systemic therapy, radiotherapy or surgery). 7) Diagnosis of any serious secondary malignancy within the last 2 years, except for adequately treated basal cell or squamous cell carcinoma of skin, or in situ carcinoma of cervix uteri or prostate cancer and curatively treated thyroid cancer of any stage. 8) Subject has known hypersensitivity to EV or to any excipient contained in the drug formulation of EV (including histidine, trehalose dihydrate, and polysorbate 20). 9) Subject has known active keratitis or corneal ulcerations 10) History of uncontrolled diabetes mellitus within 3 months of the first dose of study drug. - Uncontrolled diabetes is defined as hemoglobin A1C (HbA1c) = 8% or HbA1c between 7 and < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained. 11) Has active or uncontrolled hepatitis B or C virus infection. Participants are eligible if they: • Have been curatively treated for HCV infection as demonstrated clinically and by viral serologies. • Have received HBV vaccination with only anti-HBs positivity and no clinical signs of hepatitis. • Are HBsAg- and anti-HBc+ (ie, those who have cleared HBV after infection), or HBsAg+ with chronic HBV infection (lasting 6 months or longer) and meet conditions below. - HBV DNA viral load < 2000 IU/mL. - Have normal transaminase values, or, if liver metastases are present, abnormal transaminases, with a result of AST/ALT < 3 × ULN, which are not attributable to HBV infection. - Start or maintain antiviral treatment if clinically indicated as per the investigator. 12) Known HIV infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA load, CD4+ count = 350 cells/mm3, no history of acquired immune deficiency syndrome-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on same anti-HIV medications (meaning there are no expected further changes in that time to the number or type of antiretroviral drugs in the regimen). If an HIV infection meets the above criteria, monitoring of viral RNA load and CD4+ count is recommended. 13) Other severe acute or chronic medical or psychiatric condition that, in the opinion of the investigator, would impair the ability of the subject to receive or tolerate the planned treatment and follow-up.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-Free survival and Overall survival ;Safety | — |
Countries
Korea, Republic of
Contacts
Public Contactsoeun park
Asan Medical Center
Outcome results
None listed