RECRUITING

Enfortumab Vedotin Schedule De-escalation in Metastatic Urothelial Carcinoma

Conditions

Urothelial Carcinoma Metastatic Urothelial Carcinoma Locally Advanced Urothelial Carcinoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a non-randomized two arm open-label phase 2 pilot study in adult subjects with locally advanced or metastatic urothelial cancer. The study will investigate an alternative administration schedule of EV given as monotherapy and in combination with pembrolizumab.

Official Title

A Pilot Trial of Enfortumab Vedotin Schedule De-escalation in Metastatic Urothelial Carcinoma

Quick Facts

Study Start:2023-06-14

Study Completion:2029-07-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05923190

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Patients must have histologically and radiographically confirmed locally advanced or metastatic urothelial carcinoma. * Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v1.1 * Planned to receive EV as standard treatment for advanced urothelial cancer * ECOG performance status 0-2 * Prior systemic therapy must have completed at least 14 days prior to initiating therapy. * Age \> 18 years. * Ability to understand and willingness to sign a written informed consent and HIPAA consent document * Archival tumor biospecimen (when available) must be procured for correlative evaluation. If tumor tissue is not available or accessible despite good faith efforts, patient may still be treated on study. Formalin-fixed paraffin-embedded \[FFPE\] tissue block(s) or at least 15 unbaked, unstained slides are required. Tissue samples taken from a metastatic lesion prior to the start of screening are acceptable. * Normal organ and marrow function as defined below. * Absolute neutrophil count \> 1,000/mm3 unless patient has constitutional neutropenia * Platelets \> 100,000/ul * Hemoglobin \> 8.0 g/dL * Alanine transaminase (ALT) and aspartate transaminase (AST) \<2.5X upper limit of normal (ULN) or \<3.5X ULN if liver metastases * Creatinine Clearance \>20 ml/min * Patients must have histologically and radiographically confirmed locally advanced or metastatic urothelial carcinoma. * Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v1.1 * Planned to receive EV/pembrolizumab as standard treatment for advanced urothelial cancer * ECOG performance status 0-2 * Prior systemic therapy must have completed at least 14 days prior to initiating therapy. * Age \> 18 years. * Ability to understand and willingness to sign a written informed consent and HIPAA consent document * Archival tumor biospecimen (when available) must be procured for correlative evaluation. If tumor tissue is not available or accessible despite good faith efforts, patient may still be treated on study. Formalin fixed, paraffin embedded \[FFPE\] tissue block(s) or at least 15 unbaked, unstained slides are required. Tissue samples taken from a metastatic lesion prior to the start of screening are acceptable. * Normal organ and marrow function as defined below. * Absolute neutrophil count \> 1,000/mm3 unless patient has constitutional neutropenia * Platelets \> 100,000/ul * Hemoglobin \> 8.0 g/dL * ALT and AST \<2.5X ULN or \<3.5X ULN if liver metastases * Creatinine Clearance \>20 ml/min	* Patients who have received prior monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs) for urothelial cancer. * Grade 2 or higher baseline sensory or motor neuropathy. * Uncontrolled diabetes (HbA1c \>8%) * Patients with uncontrolled and untreated central nervous system (CNS) metastases. * Prior radiation to CNS metastases is permitted. * Prior history of CNS disease that has responded to previous systemic therapy is permitted only if no recurrence. * Patient should not have leptomeningeal disease * CNS metastases have been clinically stable for at least 6 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis. * If requiring steroid treatment for CNS metastases, the patient is on stable dose \< 20 mg/day of prednisone or equivalent for at least 2 weeks prior to starting treatment * Uncontrolled intercurrent illness including, but not limited to ongoing or active untreated infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Subjects with a history of another invasive malignancy within 3 years before the first dose of study drug that cannot be watched and requires treatment, or any evidence of residual disease from a previously diagnosed malignancy that cannot be watched and requires treatment. Adjuvant hormonal therapy for breast cancer is allowed. * Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of first dose of enfortumab vedotin. Routine antimicrobial prophylaxis is permitted. * Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with enfortumab vedotin. * History of idiopathic pulmonary fibrosis; organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. * Prior allogeneic stem cell or solid organ transplant. * Other underlying medical condition that, in the opinion of the investigator, would impair the ability of the patient to receive or tolerate the planned treatment and follow-up; any known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study. * Patients with active tuberculosis. * Pregnant or breast feeding * Patients who received prior immunotherapy for metastatic urothelial carcinoma (mUC) or for an alternative malignancy are eligible unless they developed an immune related adverse event while on therapy requiring cessation of therapy or use of disease modifying agents, corticosteroids, or immunosuppressive drugs. * History of autoimmune diseases. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, use of disease modifying agents, corticosteroids, or immunosuppressive drugs). * Patients with vitiligo or residual autoimmune hypothyroidism on stable doses of hormone replacement are permitted to enroll. * Patients with type 1 diabetes mellitus (T1DM) on a stable dose of insulin are permitted to enroll. * Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. * On high dose steroids at the time of study enrollment, defined as \>20mg prednisone (or bioequivalent), including steroids used for management of intracranial lesions. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.

Inclusion Criteria

Exclusion Criteria

* Patients must have histologically and radiographically confirmed locally advanced or metastatic urothelial carcinoma.
* Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v1.1
* Planned to receive EV as standard treatment for advanced urothelial cancer
* ECOG performance status 0-2
* Prior systemic therapy must have completed at least 14 days prior to initiating therapy.
* Age \> 18 years.
* Ability to understand and willingness to sign a written informed consent and HIPAA consent document
* Archival tumor biospecimen (when available) must be procured for correlative evaluation. If tumor tissue is not available or accessible despite good faith efforts, patient may still be treated on study. Formalin-fixed paraffin-embedded \[FFPE\] tissue block(s) or at least 15 unbaked, unstained slides are required. Tissue samples taken from a metastatic lesion prior to the start of screening are acceptable.
* Normal organ and marrow function as defined below.
* Absolute neutrophil count \> 1,000/mm3 unless patient has constitutional neutropenia
* Platelets \> 100,000/ul
* Hemoglobin \> 8.0 g/dL
* Alanine transaminase (ALT) and aspartate transaminase (AST) \<2.5X upper limit of normal (ULN) or \<3.5X ULN if liver metastases
* Creatinine Clearance \>20 ml/min
* Patients must have histologically and radiographically confirmed locally advanced or metastatic urothelial carcinoma.
* Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v1.1
* Planned to receive EV/pembrolizumab as standard treatment for advanced urothelial cancer
* ECOG performance status 0-2
* Prior systemic therapy must have completed at least 14 days prior to initiating therapy.
* Age \> 18 years.
* Ability to understand and willingness to sign a written informed consent and HIPAA consent document
* Archival tumor biospecimen (when available) must be procured for correlative evaluation. If tumor tissue is not available or accessible despite good faith efforts, patient may still be treated on study. Formalin fixed, paraffin embedded \[FFPE\] tissue block(s) or at least 15 unbaked, unstained slides are required. Tissue samples taken from a metastatic lesion prior to the start of screening are acceptable.
* Normal organ and marrow function as defined below.
* Absolute neutrophil count \> 1,000/mm3 unless patient has constitutional neutropenia
* Platelets \> 100,000/ul
* Hemoglobin \> 8.0 g/dL
* ALT and AST \<2.5X ULN or \<3.5X ULN if liver metastases
* Creatinine Clearance \>20 ml/min

* Patients who have received prior monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs) for urothelial cancer.
* Grade 2 or higher baseline sensory or motor neuropathy.
* Uncontrolled diabetes (HbA1c \>8%)
* Patients with uncontrolled and untreated central nervous system (CNS) metastases.
* Prior radiation to CNS metastases is permitted.
* Prior history of CNS disease that has responded to previous systemic therapy is permitted only if no recurrence.
* Patient should not have leptomeningeal disease
* CNS metastases have been clinically stable for at least 6 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis.
* If requiring steroid treatment for CNS metastases, the patient is on stable dose \< 20 mg/day of prednisone or equivalent for at least 2 weeks prior to starting treatment
* Uncontrolled intercurrent illness including, but not limited to ongoing or active untreated infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Subjects with a history of another invasive malignancy within 3 years before the first dose of study drug that cannot be watched and requires treatment, or any evidence of residual disease from a previously diagnosed malignancy that cannot be watched and requires treatment. Adjuvant hormonal therapy for breast cancer is allowed.
* Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of first dose of enfortumab vedotin. Routine antimicrobial prophylaxis is permitted.
* Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with enfortumab vedotin.
* History of idiopathic pulmonary fibrosis; organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
* Prior allogeneic stem cell or solid organ transplant.
* Other underlying medical condition that, in the opinion of the investigator, would impair the ability of the patient to receive or tolerate the planned treatment and follow-up; any known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study.
* Patients with active tuberculosis.
* Pregnant or breast feeding
* Patients who received prior immunotherapy for metastatic urothelial carcinoma (mUC) or for an alternative malignancy are eligible unless they developed an immune related adverse event while on therapy requiring cessation of therapy or use of disease modifying agents, corticosteroids, or immunosuppressive drugs.
* History of autoimmune diseases. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
* Patients with vitiligo or residual autoimmune hypothyroidism on stable doses of hormone replacement are permitted to enroll.
* Patients with type 1 diabetes mellitus (T1DM) on a stable dose of insulin are permitted to enroll.
* Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
* On high dose steroids at the time of study enrollment, defined as \>20mg prednisone (or bioequivalent), including steroids used for management of intracranial lesions. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.

Contacts and Locations

Study Contact

Ryan Romasko

CONTACT

2678388380

ryan.romasko@fccc.edu

Principal Investigator

Pooja Ghatalia, MD

PRINCIPAL_INVESTIGATOR

Fox Chase Cancer Center

Study Locations (Sites)

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, 19111-2497

United States

Collaborators and Investigators

Sponsor: Fox Chase Cancer Center

Pooja Ghatalia, MD, PRINCIPAL_INVESTIGATOR, Fox Chase Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-06-14

Study Completion Date2029-07-01

Study Record Updates

Study Start Date2023-06-14

Study Completion Date2029-07-01

Terms related to this study

Additional Relevant MeSH Terms

Urothelial Carcinoma
Metastatic Urothelial Carcinoma
Locally Advanced Urothelial Carcinoma