Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Adenocarcinoma

Urinary Bladder Neoplasms

Ureteral Neoplasms

Pelvic Neoplasms

Urethral Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Urethral Diseases

Ureteral Diseases

Urachal Adenocarcinoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Pembrolizumab

Immunoglobulins

Immunoconjugates

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Immunologic Factors

Patients receive enfortumab vedotin IV and pembrolizumab IV on study. Patients also undergo CT scan or MRI, and collection of blood throughout the trial.

Biospecimen Collection

Computed Tomography

Enfortumab Vedotin

Magnetic Resonance Imaging

Questionnaire Administration

Bassel Nazha, MD, MPH

Wilena Session

This phase II trial tests how well enfortumab vedotin (EV) and pembrolizumab works in treating patients with bladder cancer of variant histology (a group of less common types of bladder cancer) that have spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving enfortumab vedotin and pembrolizumab may kill more tumor cells in patients with locally advanced or metastatic bladder cancer of variant histology.

PRIMARY OBJECTIVE:

I. To evaluate the anti-tumor activity of the combination of enfortumab vedotin (EV) plus pembrolizumab by assessing the overall response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of the combination as measured by progression free survival, overall survival, and duration of response.

II. To evaluate the safety as measured by incidence of adverse events assessed up to 2 years.

EXPLORATORY OBJECTIVE:

I. To assess tissue-based assays in archival tissue and correlative changes in peripheral T-cell subsets, myeloid derived suppressor cells (MDSC), blood inflammatory markers and cytokines.

OUTLINE:

Patients receive enfortumab vedotin intravenously (IV) and pembrolizumab IV on study. Patients also undergo computed tomography (CT) scan or magnetic resonance imaging (MRI), and collection of blood throughout the trial.

Enfortumab Vedotin Plus Pembrolizumab for the Treatment of Locally Advanced or Metastatic Bladder Cancer of Variant Histology

Phase II Single-Arm Study of Enfortumab Vedotin (EV) Plus Pembrolizumab in the Treatment of Locally Advanced or Metastatic Bladder Cancer of Variant Histology

Will be measured by Response Evaluation Criteria in Solid Tumors version 1.1, and estimated by the Clopper-Pearson method with 95% confidence intervals.

Kalan-Meier method will be used to estimate median event time and 2-year survival rate with 95% confidence interval.

Determined by occurrence of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.

Graded according to the Common Terminology Criteria for Adverse Events version 5.0, and will be tabulated using descriptive statistics (mean, median, minimum, maximum, standard deviation).

National Cancer Institute (NCI)

Seagen Inc.

Astellas Pharma Inc

Merck Sharp & Dohme LLC

Emory University

Principal Investigator

Patients and caregivers receive access to the bladder cancer ENST and patients undergo psychological distress and nutrition screenings and may attend social work, psychology, and/or nutrition consultations as appropriate throughout the study. Patients, caregivers, and providers also attend virtual support group meetings periodically on study.

Assessment of Distress

Consultation Visit

Nutritional Assessment

Supportive Care

Dharmesh Gopalakrishnan

This clinical trial evaluates the impact of an education and navigation support tool (ENST) on patient and caregiver participation in care coordination for bladder cancer that has spread to nearby tissue or lymph nodes (locally advanced), to other places in the body (metastatic) or that cannot be removed by surgery (unresectable). Patients with advanced bladder cancer tend to be older, have multiple medical conditions and often have poor access to health care. An ENST may be an effective method to improve participation in treatment decision-making and care planning among patients with locally advanced, metastatic and unresectable bladder cancer and their caregivers.

PRIMARY OBJECTIVES:

I. To assess project readiness and barriers and requirements to assure success we will evaluate organizational readiness and implementation climate through stakeholder engagement.

II. Development of an ENST to meet the needs of patients and caregivers, the delivery of which is deemed feasible based on such pre-implementation assessment.

III. Implementation and delivery of the proposed ENST. IV. Facilitation of enhanced care coordination for patients with advanced bladder cancer who often have complex medical needs, using measures elaborated in the design and methods section.

V. Determining the impact of such interventions, in a quantifiable manner, using validated instruments to assess perceptions of care coordination and self-efficacy, as well as monitoring concordance with guideline-recommended care by leveraging data from a network-wide decision support tool that captures systemic therapy selections.

OUTLINE:

Patients and caregivers receive access to the bladder cancer ENST and patients undergo psychological distress and nutrition screenings and may attend social work, psychology, and/or nutrition consultations as appropriate throughout the study. Patients, caregivers, and providers also attend virtual support group meetings periodically on study.

An Education and Navigation Support Tool to Improve Participation in Care Coordination Among Patients With Locally Advanced, Metastatic and Unresectable Bladder Cancer and Their Caregivers

A Comprehensive Education and Navigational Support Program for Advanced Bladder Cancer

A 12 item instrument used to determine how well employees feel they can implement the change in process .. Each item includes a scale from 1 (Disagree ) to 5 (Agree)

Guideline-concordant care at the institutional level will be calculated as the percentage of all systemic treatment decisions captured in the Clinical Oncology Pathway.

Patient perception of care coordination will be measured using Care Coordination Instrument.

Patient perception of self-efficacy will be measured using Generalized Self-Efficacy scale. A 10 item psychometric scale with 4 choice responses ranging from 1 (not at all true) to 4 (Exactly true).

Caregiver perception of care coordination will be measured using Care Coordination Instrument for Caregivers.

Roswell Park Cancer Institute

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Melanoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Transitional Cell

Lung Neoplasms

Melanoma, Cutaneous Malignant

Skin Neoplasms

Kidney Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Kidney Diseases

Transitional Cell Carcinoma

Urethral Cancer

Neuroendocrine Tumor

Neuroepithelioma

Nivolumab

Ipilimumab

Immunoglobulin G

Immunoglobulins, Intravenous

Patients with melanoma will receive ipilimumab IV over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment with ipilimumab and nivolumab repeats every 3 weeks for 4 doses, then treatment with nivolumab repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Cohort 1 will be divided into 2 sub-groups: sub-group 1 of 25 patients, and subgroup 2 of 10 patients that will consist of varying Tocilizumab administration doses. For sub-group 1, Tocilizumab 162mg will be administered subcutaneously every 2 weeks starting week 0, up to 12 weeks for a total of 6 doses. For sub-group 2 , Tocilizumab 162mg will be administered subcutaneously once every week starting at week 0 up to week 6 followed by Tocilizumab administered subcutaneously every 2 weeks starting at week 6 up to 12 weeks for a total of 9 doses.

Patients with urothelial cancer will receive ipilimumab IV over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment with ipilimumab and nivolumab repeats every 3 weeks for 4 doses, then treatment with nivolumab repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Starting on week 1, patients also receive tocilizumab SC every 2 weeks for up to 12 weeks (6 doses) in the absence of disease progression or unacceptable toxicity.

Patients with NSCLC receive ipilimumab IV over 90 minutes every 6 weeks and nivolumab IV over 30 minutes every 2 weeks for up to 2 years. Patients also receive tocilizumab SC every 2 weeks for up to 12 weeks (6 doses). Treatment continues in the absence of disease progression or unacceptable toxicity.

Tocilizumab

Adi Diab, MD

This phase II trial investigates the side effects of tocilizumab, ipilimumab, and nivolumab in treating patients with melanoma, non-small cell lung cancer, or urothelial carcinoma that has spread to nearby tissue or lymph nodes (locally advanced). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Tocilizumab is a monoclonal antibody that may interfere with the immune system to decrease immune-related toxicities. Giving tocilizumab, ipilimumab, and nivolumab may kill more tumor cells.

PRIMARY OBJECTIVES:

I. To characterize the safety and tolerability of systemic tocilizumab, an IL-6 receptor antagonist, in combination with Ipilimumab and nivolumab as front-line treatment for patients with advanced cutaneous melanoma, urothelial carcinoma and in EGFR mutant non-small cell lung cancer (NSCLC).

II. To determine the grade 3 or higher toxicity rate of Tocilizumab in combination with Ipilimumab and nivolumab for patients with advanced cutaneous melanoma.

SECONDARY OBJECTIVES:

I. To estimate the objective response rate (ORR), defined as the proportion of patients with complete response (CR) or partial response (PR), and durable response rate (DRR), defined as the proportion of patients with objective responses of \> 6 months duration, as determined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and immune related RECIST (irRECIST).

II. To estimate progression-free survival (PFS) defined as the time from the start of treatment to disease progression or death, whichever occurs first.

III. To estimate overall survival (OS) defined as the time from the start of treatment to death from any cause.

EXPLORATORY OBJECTIVE:

I. To assess pre- and post-treatment blood/tumor biopsies for immunologic assessment and to explore any potential association between biomarker measurements and antitumor activity.

OUTLINE: OUTLINE: Patients are assigned to 1 of 3 cohorts: 1=melanoma, 2=Urothelial, 3=NSCLC.

COHORT 1: Patients with melanoma will receive ipilimumab intravenously (IV) over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment with ipilimumab and nivolumab repeats every 3 weeks for 4 doses, then treatment with nivolumab repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Cohort 1 will be divided into 2 sub-groups: sub-group 1 of 25 patients, and subgroup 2 of 10 patients that will consist of varying Tocilizumab administration doses. For sub-group 1, Tocilizumab 162mg will be administered subcutaneously every 2 weeks starting week 0, up to 12 weeks for a total of 6 doses. For sub-group 2 , Tocilizumab 162mg will be administered subcutaneously once every week starting at week 0 up to week 6 followed by Tocilizumab administered subcutaneously every 2 weeks starting at week 6 up to 12 weeks for a total of 9 doses.

COHORT 2: Patients with urothelial cancer will receive ipilimumab IV over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment with ipilimumab and nivolumab repeats every 3 weeks for 4 doses, then treatment with nivolumab repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Starting on week 1, patients also receive tocilizumab SC every 2 weeks for up to 12 weeks (6 doses) in the absence of disease progression or unacceptable toxicity.

COHORT 3: Patients with NSCLC receive ipilimumab IV over 90 minutes every 6 weeks and nivolumab IV over 30 minutes every 2 weeks for up to 2 years. Patients also receive tocilizumab SC every 2 weeks for up to 12 weeks (6 doses). Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 2 years.

Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma

A Phase II Study to Assess the Safety and Efficacy of Tocilizumab in Combination With Ipilimumab and Nivolumab in Patients With Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma

Will be summarized overall and for each tumor type using frequencies and percentages.

Will be assessed by Common Terminology Criteria for Adverse Events version 5.0. Grade 3 or greater toxicity rate will be computed along with their associated exact 95% confidence interval.

Will be defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and immune related Response Evaluation Criteria in Solid Tumors (irRECIST). Will be computed along with their associated 95% credible interval and exact 95% confidence interval.

Will be estimated using the Kaplan-Meier method. Median PFS along with its corresponding 95% confidence intervals will be presented as well as rates at specific timepoints.

Will be estimated using the Kaplan-Meier method. Median OS along with its corresponding 95% confidence intervals will be presented as well as rates at specific timepoints.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Enfortumab Vedotin Plus Pembrolizumab for the Treatment of Locally Advanced or Metastatic Bladder Cancer of Variant Histology	NCT05756569	Bladder Squamou... Locally Advance... Malignant Renal... Malignant Urete... Malignant Ureth... Metastatic Blad... Stage III Bladd... Stage IV Bladde... Unresectable Bl... Urachal Adenoca... Bladder Adenoca...	Biospecimen Col... Computed Tomogr... Enfortumab Vedo... Magnetic Resona... Pembrolizumab Questionnaire A...	18 Years -	Emory University
An Education and Navigation Support Tool to Improve Participation in Care Coordination Among Patients With Locally Advanced, Metastatic and Unresectable Bladder Cancer and Their Caregivers	NCT06414317	Locally Advance... Metastatic Blad... Stage III Bladd... Stage IV Bladde... Unresectable Bl...	Assessment of D... Consultation Vi... Nutritional Ass... Questionnaire A... Supportive Care Supportive Care	18 Years -	Roswell Park Cancer Institute
Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma	NCT04940299	Clinical Stage ... Clinical Stage ... Locally Advance... Locally Advance... Locally Advance... Locally Advance... Locally Advance... Locally Advance... Locally Advance... Malignant Solid... Metastatic Blad... Metastatic Blad... Metastatic Lung... Metastatic Mela... Metastatic Rena... Metastatic Uret... Metastatic Uret... Metastatic Uret... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Stage III Bladd... Stage III Lung ... Stage III Renal... Stage III Urete... Stage III Ureth... Stage IIIA Blad... Stage IIIA Lung... Stage IIIB Blad... Stage IIIB Lung... Stage IIIC Lung... Stage IV Bladde... Stage IV Lung C... Stage IV Renal ... Stage IV Ureter... Stage IV Urethr... Stage IVA Lung ... Stage IVB Lung ... Unresectable Me...	Ipilimumab Nivolumab Tocilizumab	18 Years -	M.D. Anderson Cancer Center
Enfortumab Vedotin Plus Pembrolizumab for the Treatment of Locally Advanced or Metastatic Bladder Cancer of Variant Histology	NCT05756569	Bladder Squamou... Locally Advance... Malignant Renal... Malignant Urete... Malignant Ureth... Metastatic Blad... Stage III Bladd... Stage IV Bladde... Unresectable Bl... Urachal Adenoca... Bladder Adenoca...	Biospecimen Col... Computed Tomogr... Enfortumab Vedo... Magnetic Resona... Pembrolizumab Questionnaire A...	18 Years -	Emory University

Spots Global Cancer Trial Database for locally advanced bladder carcinoma