Stage IV Bladder Cancer AJCC v8 Clinical Trial
Official title:
A Randomized, Phase 2 Trial to Evaluate the Safety and Efficacy of Eribulin Mesylate in Combination With Atezolizumab Compared to Atezolizumab Alone in Subjects With Locally Advanced or Metastatic Transitional Cell Urothelial Cancer Where Cisplatin-Based Treatment is Not an Option
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.
PRIMARY OBJECTIVES: I. To confirm that eribulin mesylate (eribulin), at or close to the single agent recommended phase 2 dose, and atezolizumab at the single agent recommended phase 2 dose, can be given together with an acceptable toxicity profile. (Safety/Run-in) II. To estimate the objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for eribulin and atezolizumab in combination, and compare that to the ORR of atezolizumab alone. (Phase 2) SECONDARY OBJECTIVES: I. To summarize and characterize the toxicity associated with this 2-drug combination. II. To estimate the best overall response rate (immune-related best overall response [irBOR] rate) using the immune-related response criteria (irRC). III. To estimate the disease control rate (DCR: complete response [CR] + partial response [PR] + stable disease [SD]) based on RECIST 1.1. IV. To estimate the duration of response and the duration of stable disease. V. To summarize the progression-free survival (PFS). VI. To summarize the overall survival (OS). VII. To evaluate efficacy in subsets of patients determined by PD-L1, CD3 and CD8 expression. EXPLORATORY OBJECTIVES: I. To assess the pharmacodynamic (PD) profile of eribulin when it is given in combination with atezolizumab, specifically exploring the expression of putative tumor, circulating microenvironment and computed tomography (CT) radiomic correlatives of epithelial-mesenchymal transition (EMT)/ (mesenchymal-epithelial transition) MET phenotype at baseline and 6 weeks on therapy. II. To ascertain the role of expression of PD-L1 using the SP142 assay and potentially other methods as a predictive biomarker for response to treatment with atezolizumab in combination with eribulin. III. To identify clinical biomarkers that may predict for efficacy and toxicity in this population and with this treatment combination. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive atezolizumab intravenously (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. ARM II: 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. After completion of study treatment, patients are followed up every 3 or 6 months for 52 weeks. ;
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