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Renal Retention in High Grade Upper Tract Urothelial Cancer

ConditionsHigh Grade Urothelial CarcinomaBladder CancerUrothelial Carcinoma Bladder
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorSidney Kimmel Comprehensive Cancer Center at Johns Hopkins

About this trial

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. The patients are also not candidates for metastatic trials, as the patients have no measurable metastasis. The Investigators hypothesize the combination of pembrolizumab and enfortumab vedotin for patients with high grade cN0/NxMx UTUC deferring RNU will lead to event free survival outcomes similar to that achieved by RNU in a historic dataset.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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 be diagnosed by direct visualization and biopsy, or by 3 dimensional imaging and positive urine cytology) will be enrolled in this study.

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 intra or perioperative which would adversely impact morbidity and mortality, including risk of CKD and ESRD.

Subjects who received neoadjuvant chemotherapy with recurrence >12 months from completion of therapy are permitted

Subjects that received adjuvant chemotherapy following cystectomy with recurrence >12 months from completion of therapy are permitted

Disqualifiers

Subjects who have previously received enfortumab vedotin or other MMAE-based ADCs.

Subjects 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, pembrolizumab, nivolumab, durvalumab, or avelumab).

Subjects 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).

Subjects 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 treatment (ongoing hormonal/anti hormonal treatment, e.g., for breast cancer, is allowed, provided that the subject is eligible per exclusion criteria 14).

Trial design

Design model

Single group

Treatments tested in this trial

  • Enfortumab vedotin

    Drug

    Enfortumab vedotin 1.25mg/kg on Days 1 and 8 every 3 weeks for up to 35 weeks (each cycle = 21 days)

  • Pembrolizumab

    Drug

    Pembrolizumab 200mg on Day 1 every 3 weeks for up to 35 weeks (each cycle = 21 days)

Treatment groups

20 Participants
are divided into 1 treatment group
Group A: Enfortumab vedotin with PembrolizumabExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Event free survival (EFS)

Time to relapse or death based on 12 months.

Time frame
12 months

Secondary outcomes

1

Glomerular Filtration Rate (GFR)

Change from baseline GFR to GFR 1 yr post enrollment

Time frame
Baseline, 12 months

Other outcomes

1

To evaluate safety and tolerability of the combination of enfortumab vedotin and pembrolizumab

Number of participants experiencing dose limiting toxicities and treatment-related adverse events, as defined by Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0).

Time frame
25 months
2

Progression free survival

Number of participants without disease recurrence

Time frame
48 months
3

Overall Survival

Number of participants alive end of trial.

Time frame
48 months
4

To assess feasibility of obtaining tumor for DNA sequencing including, FGFR mutation / fusion status, from UTUC biopsy specimens

Number participants with tumor available for DNA sequencing including, FGFR mutation / fusion status, from UTUC biopsy specimens

Time frame
24 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead sponsor

Source ClinicalTrials.gov
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