Atezolizumab With or Without Cobimetinib in Treating Patients With Metastatic Bile Duct Cancer That Cannot Be Removed by Surgery or Gallbladder Cancer

NCT03201458 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: NCI-2017-01127ETCTN1013910139UM1CA186691
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 41

Brief 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 (metastatic) and cannot be removed by surgery (unresectable) or gallbladder cancer. 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. Cobimetinib is used in patients whose cancer has a mutated (changed) form of a gene called BRAF. It is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving atezolizumab with cobimetinib may work better at treating patients with bile duct and gallbladder cancer.

Conditions

Gallbladder Carcinoma; Metastatic Cholangiocarcinoma; Stage III Intrahepatic Cholangiocarcinoma AJCC v8; Stage IV Intrahepatic Cholangiocarcinoma AJCC v8; Unresectable Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS within each treatment arm will be summarized descriptively and compared between groups, under the assumption of Cox proportional hazards, using the stratified log-rank test to account for tumor site. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  From date of randomization to time of progression or death, assessed up to 1 year

Secondary Outcomes (4)

• Number of Participants With Adverse Events

  Up to 1 year

• Objective Response Rate

  Up to 1 year

• Overall Survival

  From date of randomization to time of death, assessed up to 1 year

• Change in CD8+ Density Within the Tumor

  Day 21

Other Outcomes (1)

• Number of Participants With PD-L1 Expression

  Up to 1 year

Study Arms (2)

Arm A (atezolizumab)

EXPERIMENTAL

Patients receive atezolizumab IV over 30-60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and collection of blood samples throughout the trial and undergo tumor biopsy on study.

Drug: Atezolizumab; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging

Arm B (atezolizumab, cobimetinib)

EXPERIMENTAL

Patients receive atezolizumab IV over 30-60 minutes on days 1 and 15 and cobimetinib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and collection of blood samples throughout the trial and undergo tumor biopsy on study.

Drug: Atezolizumab; Procedure: Biopsy; Procedure: Biospecimen Collection; Drug: Cobimetinib; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging

Interventions

Atezolizumab DRUG

Given IV

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

Arm A (atezolizumab); Arm B (atezolizumab, cobimetinib)

Biopsy PROCEDURE

Undergo tumor biopsy

Also known as: BIOPSY_TYPE, Bx

Arm A (atezolizumab); Arm B (atezolizumab, cobimetinib)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

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

Arm A (atezolizumab); Arm B (atezolizumab, cobimetinib)

Cobimetinib DRUG

Given PO

Also known as: Cotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518

Arm B (atezolizumab, cobimetinib)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Arm A (atezolizumab); Arm B (atezolizumab, cobimetinib)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm A (atezolizumab); Arm B (atezolizumab, cobimetinib)

Eligibility Criteria

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

You may qualify if:

• 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 =\< 6 months from the last dose of adjuvant therapy in resected patients will be considered the first line of therapy)
• Includes intrahepatic cholangiocarcinoma (IHC), extrahepatic cholangiocarcinoma (EHC), and gallbladder carcinoma (GBC), but not ampulla of vater cancers
• 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 CT scan, MRI, or calipers by clinical exam; assessment must be completed within 4 weeks of randomization
• Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of cobimetinib in combination with atezolizumab in patients \< 18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 80%)
• Life expectancy of greater than 2 months
• Leukocytes \>= 2,500/mcL (within 2 weeks of randomization)
• Absolute neutrophil count \>= 1,500/mcL (within 2 weeks of randomization)
• Platelets \>= 75,000/mcL (within 2 weeks of randomization)
• Hemoglobin \>= 8 g/dL (within 2 weeks of randomization)
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =\< 3 x ULN may be enrolled) (within 2 weeks of randomization)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x ULN (within 2 weeks of randomization)
• Creatinine clearance \>= 30 mL/min/1.73 m\^2 by Cockcroft-Gault OR creatinine \< 1.5 x ULN (within 2 weeks of randomization)
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose) (within 2 weeks of randomization)
• Administration of atezolizumab and cobimetinib may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; women of childbearing potential must agree to use either two adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy, or to abstain from heterosexual activity (complete abstinence) prior to study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of study agent; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; male patients must agree to use an adequate method of contraception, or to abstain from heterosexual activity (complete abstinence), prior to study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of study agent

You may not qualify if:

• Received chemotherapy or radiotherapy within 3 weeks prior to randomization or those who have not recovered to =\< grade 1 adverse events (other than alopecia) due to agents administered more than 3 weeks earlier; herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to randomization; for patients who received prior immunotherapy (eg anti-CTLA-4), at least five drug half-lives must have passed before the patient may enroll on this study; however, the following therapies are allowed:
• Hormone-replacement therapy or oral contraceptives
• Palliative radiotherapy for bone metastases \>= 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 (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) 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, with the following exceptions:
• Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:
• Radiographic demonstration of clinical stability upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study
• No stereotactic radiation or whole-brain radiation within 28 days prior to randomization
• Screening CNS radiographic study \>= 4 weeks from completion of radiotherapy and \>= 2 weeks from discontinuation of corticosteroids
• Has a 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; superficial bladder cancer, non-melanoma skin cancers, or low grade prostate cancer not requiring therapy should not exclude participation in this trial

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (41)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Smilow Cancer Hospital-Derby Care Center

Derby, Connecticut, 06418, United States

Location

Smilow Cancer Hospital Care Center-Fairfield

Fairfield, Connecticut, 06824, United States

Location

Smilow Cancer Hospital Care Center - Guilford

Guilford, Connecticut, 06437, United States

Location

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, 06105, United States

Location

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Yale-New Haven Hospital North Haven Medical Center

North Haven, Connecticut, 06473, United States

Location

Smilow Cancer Hospital-Torrington Care Center

Torrington, Connecticut, 06790, United States

Location

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, 06611, United States

Location

Smilow Cancer Hospital-Waterbury Care Center

Waterbury, Connecticut, 06708, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376, United States

Location

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States

Location

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, 63136, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Related Publications (1)

• Yarchoan M, Cope L, Ruggieri AN, Anders RA, Noonan AM, Goff LW, Goyal L, Lacy J, Li D, Patel AK, He AR, Abou-Alfa GK, Spencer K, Kim EJ, Davis SL, McRee AJ, Kunk PR, Goyal S, Liu Y, Dennison L, Xavier S, Mohan AA, Zhu Q, Wang-Gillam A, Poklepovic A, Chen HX, Sharon E, Lesinski GB, Azad NS. Multicenter randomized phase II trial of atezolizumab with or without cobimetinib in biliary tract cancers. J Clin Invest. 2021 Dec 15;131(24):e152670. doi: 10.1172/JCI152670.

  PMID: 34907910 DERIVED

MeSH Terms

Conditions

Gallbladder Neoplasms; Cholangiocarcinoma

Interventions

atezolizumab; Biopsy; Specimen Handling; cobimetinib; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Results Point of Contact

• Title: Grants Administrative Manager
• Organization: Johns Hopkins University

JHCCCRO@jhmi.edu

4439273568

Study Officials

• Nilofer S Azad

  JHU Sidney Kimmel Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

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: June 27, 2017
• First Posted: June 28, 2017
• Study Start: February 8, 2018
• Primary Completion: August 7, 2020
• Study Completion: February 19, 2024
• Last Updated: April 5, 2024
• Results First Posted: July 11, 2023

Record last verified: 2024-02

Locations

US (41)