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Clinical Trial 19597

Cancer Type:
Interventions:Atezolizumab (Tecentriq); Cobimetinib

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Richard Kim

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

A Randomized Phase 2 Study of Atezolizumab in Combination with Cobimetinib versus Atezolizumab Monotherapy in Participants with resectable Cholangiocarcinoma

Summary

This randomized phase II trial studies how well atezolizumab with or without cobimetinib works in treating patients with bile duct cancer that has spread to other places in the body and cannot be removed by surgery or gallbladder cancer. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. Cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab with cobimetinib may work better at treating patients with bile duct and gallbladder cancer.

Objective

1.1 Primary Objectives: 1.1.1 To assess the progression free survival (PFS) of patients receiving atezolizumab monotherapy and cobimetinib in combination with atezolizumab for unresectable cholangiocarcinoma. 1.2 Secondary Objectives: 1.2.1 To assess the overall survival (OS) of patients receiving cobimetinib in combination with atezolizumab and atezolizumab monotherapy for unresectable cholangiocarcinoma. 1.2.2 To determine the objective response rate (ORR), defined as complete plus partial response, of cobimetinib in combination with atezolizumab and atezolizumab monotherapy in patients with unresectable cholangiocarcinoma. 1.2.3 To assess the safety and tolerability of cobimetinib in combination with atezolizumab and atezolizumab monotherapy in patients with unresectable cholangiocarcinoma. 1.2.4 To determine the relationship between PD-L1 expression in tumor at baseline and on treatment, and response to treatment. 1.3 Correlative Objectives: 1.3.1 To determine the effect of cobimetinib on CD8+ T cell infiltration in tumor. 1.3.2 To determine the effect of cobimetinib on T cell subpopulations systemically and in tumor, PD-1/PD-L1 expression on tumor, and MHC 1/2 expression. 1.3.3 To determine the effect of cobimetinib on markers of immune exhaustion and proapoptotic factors in CD8+ effector T cells. 1.3.4 To explore the effect of cobimetinib on local and systemic immune activation pathways and immune suppressive pathways through expression profiling.

Inclusion Criteria

  • Pathologically confirmed metastatic or unresectable cholangiocarcinoma or gallbladder carcinoma (GBC), having received at least 1 prior line of systemic therapy, and received no more than 2 prior lines of therapy in the metastatic setting (disease recurrence > Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam; assessment must be completed within 4 weeks of randomization
  • Eastern Cooperative Oncology Group (ECOG) performance status == 80%)
  • Life expectancy of greater than 2 months
  • Adequate organ function.
  • Women of childbearing and males must adhere to contraception guidelines.
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients positive for human immunodeficiency virus (HIV) are allowed on study, but HIV-positive patients must have: A stable regimen of highly active anti-retroviral therapy (HAART); No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections; A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard polymerase chain reaction (PCR)-based tests.

  • Exclusion Criteria

  • Received chemotherapy or radiotherapy within 3 weeks prior to randomization or those who have not recovered to == 2 weeks prior to randomization.
  • Prior treatment with a MEK inhibitor or ERK inhibitor
  • Prior treatment with any anti-PD-1 or anti-PD-L1 antibody, prior allogeneic bone marrow transplantation, or prior solid organ transplantation
  • Treatment with any investigational agent within 4 weeks prior to cycle 1, day 1, or five drug half-lives (whichever is longer)
  • Treatment with systemic immunosuppressive medications within 6 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 with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases. Some exceptions may apply.
  • Known concurrent malignancy that is expected to require active treatment within two years, or may interfere with the interpretation of the efficacy and safety outcomes of this study in the opinion of the treating investigator.
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • Allergy or hypersensitivity to components of the cobimetinib formulations
  • History of congenital long QT syndrome or corrected QT interval (QTc) > 450 msec within 2 weeks of randomization
  • Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) or below 50%, whichever is lower, as determined by echocardiogram or multi-gated acquisition (MUGA) scan within 4 weeks of randomization
  • Known risk factors for ocular toxicity.
  • Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 enzymes.
  • Known clinically significant liver disease.
  • History or risk of autoimmune disease. Some exceptions may apply.
  • History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Severe infections within 4 weeks prior to randomization.
  • Signs or symptoms of infection within 2 weeks prior to randomization
  • Received oral or intravenous (IV) antibiotics within 2 weeks prior to randomization; patients receiving prophylactic antibiotics are eligible.
  • Major surgical procedure within 4 weeks prior to randomization or anticipation of need for a major surgical procedure during the course of the study
  • Uncontrolled intercurrent illness.
  • Women who are pregnant or breastfeeding.
  • Inability or unwillingness to swallow pills
  • History of malabsorption syndrome or other condition that would interfere with enteral absorption.
  • Clinically significant ascites, defined as ascites that is symptomatic or has resulted in a paracentesis in the past 3 months