Atezolizumab With or Without Eribulin Mesylate in Treating Patients With Recurrent Locally Advanced or Metastatic Urothelial Cancer

NCT03237780 | Active Not Recruiting Phase 2 FDA Drug

• 4 other identifiers: NCI-2017-01388PHII-15010100UM1CA186717
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 21

Brief Summary

This phase II trial studies the side effects of atezolizumab with or without eribulin mesylate and how well they work in treating patients with urothelial cancer that has come back (recurrent), spread to nearby tissues or lymph nodes (locally advanced), or spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving atezolizumab and eribulin mesylate may work better at treating urothelial cancer compared to atezolizumab alone.

Conditions

Locally Advanced Urethral Urothelial Carcinoma; Stage IV Renal Pelvis Cancer AJCC v8; Unresectable Ureter Urothelial Carcinoma; Unresectable Urethral Urothelial Carcinoma; Metastatic Urethral Urothelial Carcinoma; Stage III Bladder Cancer AJCC v8; Metastatic Bladder Urothelial Carcinoma; Metastatic Renal Pelvis Urothelial Carcinoma; Stage IV Bladder Cancer AJCC v8; Metastatic Ureter Urothelial Carcinoma; Stage III Ureter Cancer AJCC v8; Stage IV Ureter Cancer AJCC v8; Unresectable Bladder Urothelial Carcinoma; Recurrent Bladder Urothelial Carcinoma; Recurrent Renal Pelvis Urothelial Carcinoma; Recurrent Ureter Urothelial Carcinoma; Recurrent Urethral Urothelial Carcinoma; Stage III Urethral Cancer AJCC v8; Stage IV Urethral Cancer AJCC v8; Unresectable Renal Pelvis Urothelial Carcinoma; Locally Advanced Bladder Urothelial Carcinoma; Locally Advanced Renal Pelvis Urothelial Carcinoma; Stage III Renal Pelvis Cancer AJCC v8; Locally Advanced Ureter Urothelial Carcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (Safety/Run-In)

  Will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5. Tables will be created to summarize the numbers of patients who experienced toxicities by arm, toxicity system, type, grade and attribution. If helpful, cumulative incidence curves will be constructed to summarize the onset of selected adverse events.

  Up to 52 weeks

• Overall response rate (probability of complete response [CR] or partial response [PR]) (Phase II)

  Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The two arms will be compared using a one-sided, 0.10-level Mantel-Haenszel, stratifying by (a) cisplatin ineligible first line vs. having received prior platinum therapy, and PD-L1 status in archival tumor tissue (immunohistochemistry \[IHC\] 0-1 versus \[vs\] 2-3). Two-sided 80% confidence intervals will be constructed for the probability of response in each arm, as well as the difference between the two arms (unadjusted for the stratification variables). In addition, a logistic regression (exact, if required based on the numbers) will be used to estimate the odds ratio comparing the 2 arms adjusting for the stratification variables, and also by the Bellmunt risk group (1-2 versus \[vs\] 3-4).

  Up to 52 weeks

Secondary Outcomes (7)

• Incidence of adverse events

  Up to 52 weeks

• Best overall response rate (immune-related best overall response [irBOR] rate) using the immune-related response criteria

  Up to 52 weeks

• Disease control rate (DCR: CR + PR + stable disease)

  Up to 52 weeks

• Progression-free survival (PFS)

  From randomization until progression or death, whichever occurs first, assessed up to 52 weeks

• Overall survival (OS)

  From randomization until death or date last known to be alive, assessed up to 52 weeks

Other Outcomes (2)

• Analysis of baseline tumor

  Baseline

• Changes in tumor based on biopsies, radiomics and circulating tumor cells

  Baseline up to 6 weeks

Study Arms (2)

Arm I (atezolizumab)

EXPERIMENTAL

Patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and CT with contrast throughout the trial. Patients may undergo biopsy during screening and on study.

Drug: Atezolizumab; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography with Contrast

Arm II (atezolizumab, eribulin mesylate)

EXPERIMENTAL

Patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle and eribulin mesylate IV over 2-3 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and CT with contrast throughout the trial. Patients may undergo biopsy during screening and on study.

Drug: Atezolizumab; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography with Contrast; Drug: Eribulin Mesylate

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (atezolizumab); Arm II (atezolizumab, eribulin mesylate)

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Arm I (atezolizumab); Arm II (atezolizumab, eribulin mesylate)

Computed Tomography with Contrast PROCEDURE

Undergo CT scan

Also known as: Contrast Enhanced Computed Tomography, CONTRAST ENHANCED CT SCAN, Contrast-enhanced Computed Tomography, CT Scan With Contrast, CT with Contrast

Arm I (atezolizumab); Arm II (atezolizumab, eribulin mesylate)

Eribulin Mesylate DRUG

Given IV

Also known as: B1939 Mesylate, E7389, ER-086526 Mesylate, Halaven, Halichondrin B Analog

Arm II (atezolizumab, eribulin mesylate)

Atezolizumab DRUG

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG 7446, RG-7446, RG7446, RO 5541267, RO-5541267, RO5541267, Tecentriq

Arm I (atezolizumab); Arm II (atezolizumab, eribulin mesylate)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females age \> or = 18 years at the time of informed consent. Because no dosing or adverse event data are currently available on the use of atezolizumab in combination with eribulin in patients \< 18 years of age, children are excluded from this study
• Histologically- or cytologically-confirmed diagnosis of locally advanced/unresectable (inoperable or not amenable to surgical treatment) and/or metastatic transitional cell urothelial cancer of the renal pelvis, ureter, urinary bladder, or urethra
• Presence of measurable disease meeting the following criteria:
• At least one lesion of \>= 1.0 cm in long axis diameter for non-lymph nodes or \>= 1.5 cm in short axis diameter for lymph nodes that is serially measurable according to RECIST 1.1 using either computerized tomography or magnetic resonance imaging or panoramic and close-up color photography with caliper measurement; if there is only one target lesion and it is a not a lymph node, it should have a long-axis diameter of at least 1.5 cm
• Lesions that have had radiotherapy must show radiographic evidence of disease progression based on RECIST 1.1 may be deemed a target lesion
• Archival paraffin-embedded invasive tumor tissue or newly obtained biopsy must be available prior to the first dose of study drug for biomarker analysis; patients must be offered sequential biopsies at baseline and 6 weeks unless in the opinion of the trial principal investigator (PI) this would be hazardous; recent data suggest discordance between primary tumor and tumor from recurrence or metastasis with high percentages of PD-L1 SP142 positive immune cells after recurrence
• PD-L1 status determined centrally by HistogeneX, which is funded by the study, must be available before randomization of the patient to allow for stratification; COMMERCIAL ASSESSMENT OF PD-L1 STATUS OBTAINED LOCALLY AT THE SITE WILL NOT SATISFY ELIGIBILITY CRITERIA
• New, progressive or recurrent disease occurring
• During or within 12 months of treatment with a platinum containing regimen (cisplatin or carboplatin or novel platinum) in either in the metastatic or perioperative setting
• In first-line patients defined as cisplatin-ineligible based on renal impairment (creatinine clearance calculated by Cockcroft-Gault method \< 60 ml/min), at least grade 2 hearing loss and/or Eastern Cooperative Oncology Group (ECOG) status of 2; these patients will be chemotherapy naive or have received platinum based therapy in the adjuvant or neoadjuvant setting more than 12 months prior to study entry
• May have received up to two prior lines of chemotherapy for advanced disease
• Adequate recovery from any adverse events resulting from prior anti-neoplastic treatment including chemotherapy, biological therapy, targeted small molecule therapy, radiation therapy, and surgery as determined by the investigator (and in consultation with the study PI); in most instances, adequate recovery is resolution to =\< grade 1 except for alopecia of any grade, grade 2 neuropathy and/ or any grade hearing loss
• Subjects with known brain metastases will be eligible if they have completed the primary brain therapy (such as whole brain radiotherapy, stereotactic radiosurgery, or complete surgical resection) and if they have remained clinically stable, asymptomatic, and off of steroids for at least 28 days
• Life expectancy of \>= 12 weeks
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky \>= 60%)

You may not qualify if:

• Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
• Patients who have had chemotherapy within 3 weeks or radiotherapy or targeted therapy 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (other than alopecia) due to agents administered more than 4 weeks earlier; however, the following therapies are allowed:
• Hormone-replacement therapy or oral contraceptives
• Herbal therapy \> 1 week prior to cycle 1, day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to cycle 1, day 1)
• Palliative radiotherapy for bone metastases \> 2 weeks prior to cycle 1, day 1
• Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents or eribulin
• Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:
• Minimum of 12 weeks from the first dose of anti-CTLA-4 and \> 6 weeks from the last dose
• No history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0)
• Treatment with any other investigational agent within 4 weeks prior to cycle 1, day 1
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon \[IFN\]-alpha or interleukin \[IL\]-2) within 6 weeks prior to cycle 1, day 1
• Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to cycle 1, day 1
• Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled
• The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
• Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (21)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Keck Medicine of USC Buena Park

Buena Park, California, 90621, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

Location

Keck Medicine of USC Koreatown

Los Angeles, California, 90020, United States

Location

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

USC Norris Oncology/Hematology-Newport Beach

Newport Beach, California, 92663, United States

Location

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

Keck Medical Center of USC Pasadena

Pasadena, California, 91105, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

City of Hope Upland

Upland, California, 91786, United States

Location

University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, 66210, United States

Location

University of Kansas Hospital-Indian Creek Campus

Overland Park, Kansas, 66211, United States

Location

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

Location

University of Kansas Cancer Center - North

Kansas City, Missouri, 64154, United States

Location

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, 64064, United States

Location

University of Kansas Cancer Center at North Kansas City Hospital

North Kansas City, Missouri, 64116, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Ureteral Neoplasms; Urethral Neoplasms

Interventions

atezolizumab; Biopsy; Specimen Handling; Contrast Media; eribulin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Ureteral Diseases; Urethral Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Diagnostic Uses of Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals

Study Officials

• Anishka A D'Souza

  City of Hope Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2017
• First Posted: August 3, 2017
• Study Start: July 20, 2018
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 13, 2026

Record last verified: 2025-12

Locations

US (21)