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New treatment option for High Grade Urothelial Carcinoma
Official title Renal Retention in High Grade Upper Tract Urothelial Cancer
ClinicalTrials.gov ID: NCT05656235
What this study is testing
What is Enfortumab vedotin?
Enfortumab vedotin is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for high grade urothelial carcinoma.
Also referred to as Padcev.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This trial will evaluate the use of combination pembrolizumab and enfortumab vedotin for patients with high grade non-metastatic (cN0/NxMx, no measurable regional lymph nodes, no metastases) upper tract urothelial cancer (UTUC), preferring to forego standard of care radical nephroureterectomy (RNU) surgery. Currently these patients would not be suitable candidates for neoadjuvant trials, as the patients intention is to forego surgery.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of...
- Patients must refuse definitive radical nephroureterectomy (RNU), or be medically ineligible for surgery. To be medically ineligible, patients must...
- people must not have received prior systemic therapy for locally advanced or metastatic urothelial carcinoma (in other locations such as the bladder...
- people who received neoadjuvant chemotherapy with recurrence \>12 months from completion of therapy are permitted
- people that received adjuvant chemotherapy following cystectomy with recurrence \>12 months from completion of therapy are permitted
You likely can't join if
- people who have previously received enfortumab vedotin or other MMAE-based ADCs.
- people who have received prior treatment with a PD-(L)-1 inhibitor for any malignancy, including earlier stage UC, defined as a PD-1 inhibitor or...
- people who have previously received any prior treatment with an agent directed to another stimulatory or co inhibitory T-cell receptor (including but...
- people who have received anti-cancer treatment with chemotherapy, biologics, or investigational agents not otherwise prohibited by exclusion...
- people with uncontrolled diabetes. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c 7% to \<8% with associated diabetes...
- people with an estimated life expectancy \<12 weeks
See the full eligibility criteria
Who can join
- Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of histologically documented, high grade upper tract urothelial cancer, (UTUC can...
- Patients must refuse definitive radical nephroureterectomy (RNU), or be medically ineligible for surgery. To be medically ineligible, patients must, in the opinion of the clinical team, be at high risk of complications...
- people must not have received prior systemic therapy for locally advanced or metastatic urothelial carcinoma (in other locations such as the bladder or contralateral ureter or renal pelvis) with the following exceptions:
- people who received neoadjuvant chemotherapy with recurrence \>12 months from completion of therapy are permitted
- people that received adjuvant chemotherapy following cystectomy with recurrence \>12 months from completion of therapy are permitted
- people may have radiographic evidence of N1 disease (Metastasis ≤2 cm in greatest dimension, in a single lymph node)
- people must be age 18 years or older.
- Archival tumor tissue will be used for eligibility.
- people must have an ECOG Performance Status score of 0 or 2
- people must have adequate hematologic and organ function as defined by the baseline laboratory values in Table 3. Transfusion of red blood cells to meet eligibility criteria is allowed. Table 3 - Baseline Laboratory...
- A female subject of childbearing potential is anyone born female who has experienced menarche and who has not undergone surgical sterilization (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or has...
- Agree not to try to become pregnant during the study and for at least 6 months after the final dose of study drug.
- Must have a negative urine or serum pregnancy test (minimum sensitivity of 25 mIU/mL or equivalent units of beta human chorionic gonadotropin [β-hCG]) within 1 day prior to administration of study drug. Female people...
- If heterosexually active, must consistently use highly effective methods of birth control, with a failure rate of less than 1% (as described in Appendix L) starting at screening, throughout the study period, and for at...
- Female people must agree not to breastfeed or donate ova starting at screening and throughout the study period, and for at least 6 months after the final dose of study drug.
- A male subject who can father children is anyone born male who has testes and who has not undergone surgical sterilization (e.g., vasectomy followed by a clinical test proving that the procedure was effective). Male...
- Must not donate sperm starting at screening and throughout the study period, and for at least 6 months after the final dose of study drug. Male people will be informed about the negative risk to reproductive function...
- Must consistently use highly effective methods of birth control, with a failure rate of less than 1% (as described in Appendix L) starting at screening and continue throughout study period and for at least 6 months...
- Male people with a pregnant or breastfeeding partner(s) must consistently use one of 2 contraception options for preventing secondary exposure to seminal fluid (as described in Appendix L) for the duration of the...
- people must provide written informed consent.
What rules you out
- people who have previously received enfortumab vedotin or other MMAE-based ADCs.
- people who have received prior treatment with a PD-(L)-1 inhibitor for any malignancy, including earlier stage UC, defined as a PD-1 inhibitor or PD-L1inhibitor (including, but not limited to, atezolizumab...
- people who have previously received any prior treatment with an agent directed to another stimulatory or co inhibitory T-cell receptor (including but not limited to CD137 agonists, CTLA-4 inhibitors, or OX-40 agonists).
- people who have received anti-cancer treatment with chemotherapy, biologics, or investigational agents not otherwise prohibited by exclusion criterion 1-3 that is not completed 4 weeks prior to first dose of study...
- people 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.
- people with an estimated life expectancy \<12 weeks
- people with ongoing sensory or motor neuropathy Grade 2 or higher.
- people with ongoing clinically significant toxicity associated with prior treatment (including radiotherapy or surgery) that has not resolved to ≤ Grade 1 or returned to baseline.
- Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of treatment initiation. Routine antimicrobial prophylaxis is permitted.
- people who have known active hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] detected) infection, testing for hepatitis B and hepatitis C is required if...
- Has a known history of human immunodeficiency virus (HIV) infection. Testing is not required unless mandated by the local health authority.
- people with conditions requiring high doses of steroids (\>10 mg/day of prednisone or equivalent) or other immunosuppressive medications are excluded. Inhaled or topical steroids are permitted in the absence of active...
- people with another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer. people that have completed all necessary therapy and are considered to be at less than 30% risk...
- Patients may have a history of resected urothelial cancer of the bladder or contralateral upper tract, (including neoadjuvant chemotherapy) in the following categories. These disease states are not exclusions and...
- pT0, Tis, or T1N0 and have no evidence of disease (NED) for more than 2 years from surgery or chemotherapy;
- pT2-3aN0 and NED for more than 3 years from surgery or chemotherapy; or
- \>pT3b, or N+ and NED for more than 5 years from surgery or chemotherapy.
- Patients with concomitant HG UTUC bilaterally will be considered for protocol on a case by case basis.
- people with a documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with NYHA Class IV within 6 months prior to...
- people who have received radiotherapy within 2 weeks prior to treatment initiation. Subject must have recovered adequately from the toxicity from the intervention prior to starting study treatment. Participants must...
- people who have received major surgery within 4 weeks prior to treatment initiation. Subject must have recovered adequately from complications from the intervention prior to starting study treatment.
- people with known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin (including histidine, trehalose dihydrate, and polysorbate 20). people...
- people with active keratitis or corneal ulcerations. people with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator.
- History of autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
- Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
- Brief (\<7 days) use of systemic corticosteroids is allowed when use is considered standard of care.
- people with vitiligo, psoriasis, type 1 diabetes mellitus, hypothyroidism, or resolved childhood asthma/atopy will not be excluded.
- people requiring intermittent use of bronchodilators, inhaled steroids, or local steroid injections will not be excluded.
- people with hypothyroidism that is stable with hormone replacement or Sjögren's syndrome will not be excluded.
- people with a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. Has a history of...
- people who have received a prior allogeneic stem cell or solid organ transplant. people who have received a live vaccine or live-attenuated vaccine within 30 days prior to treatment initiation. Administration of killed...
- Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
- people with active tuberculosis
- people with another underlying medical 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; any known psychiatric or...
The study team makes the final eligibility decision.
Where it's taking place
- Washington D.C., District of Columbia, United States
- Baltimore, Maryland, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Washington D.C., District of Columbia, United States; Baltimore, Maryland, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.