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Study of Atezolizumab + Bevacizumab in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by Toni Choueiri, MD, Dana-Farber Cancer Institute
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Toni Choueiri, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT02724878
First received: March 16, 2016
Last updated: May 2, 2017
Last verified: May 2017
  Purpose
This research study is studying the combination of Atezolizumab and Bevacizumab as a possible treatment for Advanced Non-Clear Cell Kidney Cancer.

Condition Intervention Phase
Advanced Non-Clear Cell Kidney Cancer Drug: Bevacizumab Drug: Atezolizumab Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Atezolizumab + Bevacizumab in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Toni Choueiri, MD, Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Overall response rate [ Time Frame: 2 years ]

Secondary Outcome Measures:
  • Duration of response [ Time Frame: 2 years ]
  • Number of participants with treatment-related adverse events assessed by CTCAE version 4.0 [ Time Frame: 2 years ]
  • Immune related objective response rate [ Time Frame: 2 years ]
  • Progression free survival [ Time Frame: 2 years ]
  • Overall survival [ Time Frame: 2 years ]
  • Function Assessment of Cancer Therapy-Kidney Symptom Index-19 score [ Time Frame: 2 years ]
  • Brief Fatigue Inventory score [ Time Frame: 2 years ]

Other Outcome Measures:
  • Presence of programmed death-ligand 1 tumor expression by immunohistochemistry [ Time Frame: 2 years ]

Estimated Enrollment: 40
Study Start Date: April 2016
Estimated Study Completion Date: October 2023
Estimated Primary Completion Date: October 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab And Atezolizumab Combination
Patients will be administered a pre-determine dose of Bevacizumab and Atezolizumab intravenously every 3 weeks. Patients will be evaluated clinically every 3 weeks and will undergo disease assessments with imaging every 6 weeks.
Drug: Bevacizumab
Monoclonal antibody that binds circulating vascular endothelial growth factor
Other Name: Avastin
Drug: Atezolizumab
Monoclonal antibody that binds programmed death ligand-1
Other Name: RG-7446

Detailed Description:

This research study is a Phase II clinical trial. In this research the investigators are studying the combination of Atezolizumab with Bevacizumab. Participants will receive both vascular endothelial targeted therapy and immunotherapy.

The FDA (the U.S. Food and Drug Administration) has not approved Atezolizumab for Advanced Non-Clear Cell Kidney Cancer, but it has been approved for other uses.

The FDA has approved Bevacizumab with Interferon (IFNα) as a treatment option for Advanced Kidney Cancer.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Unresectable advanced or metastatic non-clear cell renal cell carcinoma to include but not limited to:

    • Papillary renal cell carcinoma, any type
    • Unclassified renal cell carcinoma
    • Translocation renal cell carcinoma
    • Chromophobe renal cell carcinoma
    • Collecting duct renal cell carcinoma
    • Medullary renal cell carcinoma
    • Clear cell renal cell carcinoma or any histology with ≥ 20% sarcomatoid features will be eligible.
    • Other non-clear cell histologies that are not included above need to be discussed with the Principal Investigator.
  • Request for formalin-fixed, paraffin-embedded (FFPE) archival tumor specimens if available and willingness of the participant to undergo mandatory fresh tumor biopsy unless determined medically unsafe or not feasible. Participants with no available archival tumor tissue will be required to undergo a fresh tumor biopsy at baseline. A note from the study team should be provided documenting availability of tissue.

    • The archival specimen should contain adequate viable tumor tissue.
    • The specimen may consist of a tissue block (preferred and should contain the highest grade of tumor) or at least 30 unstained serial sections. Fine-needle aspiration, brushings, cell pellet from pleural effusion, bone marrow aspirate/biopsy are not acceptable.
    • Fresh tumor biopsy at progression will be required in cases where patients experience relapse after an initial response if medically safe.
  • Measurable disease as defined by Response Evaluation Criteria In Solid Tumors version 1.1.
  • Eastern Cooperative Oncology Group performance status ≤ 2.
  • Adequate hematologic and end-organ function as defined by the following laboratory results obtained within 28 days prior to the first study treatment:

    • Absolute neutrophil count ≥ 1500 cells/uL.
    • Lymphocyte count ≥ 500/uL.
    • Platelet count ≥ 100,000/uL.
    • Hemoglobin ≥ 9 g/dL (patients may be transfused to meet this criterion).
    • Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal with the following exceptions: Patients with documented liver metastases should have aspartate aminotransferase and alanine aminotransferase ≤ 5 x upper limit of normal.
    • Serum bilirubin ≤ 2.0 x upper limit of normal with the following exception: Patients with known Gilbert's disease should have a serum bilirubin ≤ 3 x upper limit of normal.
    • Serum albumin > 2.5 g/dL.
    • Creatinine clearance ≥ 30 mL/min as calculated by Cockcroft-Gault equation.
  • For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective forms of contraception and to continue its use 6 months after the last dose of atezolizumab or bevacizumab.
  • Signed informed consent form.
  • Ability and capacity to comply with study and follow-up procedures.

Exclusion Criteria:

  • Prior treatment with CD137 agonists, anti- cytotoxic T-lymphocyte-associated protein 4, anti-programmed death-1, or anti-programmed death ligand-1 therapeutic antibody or pathway targeting agents.
  • Prior interferon alpha or interleukin-2 is allowed following 4 week washout from treatment start.
  • Prior therapy with Bevacizumab.
  • Thrombologics event within 3 weeks of treatment start date or stability of anticoagulation for 2 weeks.
  • Treatment with systemic immunosuppressive medications including but not limited to: prednisone, dexamethasone, cyclosporin, azathioprine, methotrexate, thalidomide, anti-tumor necrosis factor agents, hydroxychloroquine within 2 weeks of first study dose.

    • Patients who have received acute, low-dose systemic immunosuppressant medications may be enrolled.
    • Patients with adrenal insufficiency on physiologic replacement doses of steroids may be enrolled.
    • The use of inhaled, topical intraocular, or intraarticular corticosteroids ormineralocorticoids are allowed.
  • Radiotherapy for renal cell carcinoma within 14 days of first study treatment with the exception of a single fraction of radiation administered for palliation of symptoms.
  • Known active metastases to the brain, spinal cord or leptomeninges unless adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks of first study treatment as documented by magnetic resonance imaging or computerized tomography imaging and having no ongoing requirement for steroids.
  • Malignancies other than renal cell carcinoma within 2 years of first study treatment with the exception of those with negligible risk of metastases or death (carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ of the breast, non-muscle invasive urothelial carcinoma, or other malignancy not deemed to impact that patients 5-year life expectancy. Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. In addition, individuals with the following cancer are eligible regardless of when they were diagnosed and treated: cervical cancer in situ, basal cell or squamous cell carcinoma of the skin.
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein.
  • Known hypersensitivity to any component of the Atezolizumab product.
  • History of autoimmune disease including: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, type I diabetes mellitus, vasculitis, or glomerulonephritis. Patients with a history of autoimmune-related hypothyroidism on a stable dose (without adjustment in 4 week of first study treatment) of thyroid replacement hormone are eligible.
  • History of idiopathic pulmonary fibrosis, organized pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening imaging of the chest. History of radiation pneumonitis in the radiation field is permitted.
  • Positive test for HIV (test to be performed within 28 days of first treatment start).
  • Patients with active or chronic hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening). Patients with past/resolved HBV infection (defined as having negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. A negative HBA DNA test must be obtained in patients with positive hepatitis B core antibody prior to Cycle 1 Day 1.
  • Active hepatitis C infection. Patients positive hepatitis C antibody test are eligible if PCR is negative for hepatitis C viral DNA.
  • Infection requiring receipt of therapeutic oral or IV anti-microbials within 2 weeks of first study treatment. Patients receiving routine anti-microbial prophylaxis (for dental extractions/procedures) are eligible.
  • Significant cardiovascular disease such as New York Heart Association class II or greater, myocardial infarction within the previous 3 months of first study treatment, unstable arrhythmias, unstable angina. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist when appropriate.
  • Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg). Anti-hypertensive therapy to achieve these parameters is allowed.
  • Prior history of hypertensive crisis or hypertensive encephalopathy within the previous 3 months of first study treatment.
  • History of stroke or transient ischemic attack within 3 months of first study dose.
  • Significant vascular disease (such as aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months of first study dose.
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
  • Current or recent use of dipyramidole, ticlopidine, clopidogrel, cilostazol is excluded. Aspirin (≤ 325 mg per day) is allowed.
  • Prophylactic anticoagulation with oral or parenteral anticoagulants for the patency of venous access devices or other indications is allowed.
  • Therapeutic use of low-molecular weight heparin (such as enoxaparin) is allowed.
  • History of abdominal or tracheoesophageal fistula or gastrointestinal perforation within 6 months of first study treatment.
  • Clinical signs or symptoms of active gastrointestinal obstruction or requirement of routine parenteral nutrition or tube feedings.
  • Evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
  • Serious, non-healing or dehiscing wound, or active ulcer.
  • Proteinuria, as demonstrated by > 1.5 gram of protein in a 24-hour urine collection. All patients with ≥ 2+ protein on dipstick urinalysis at baseline must undergo 24-hour urine collection for protein.
  • Major surgical procedure within 21 days of first study treatment.
  • Prior allogenic stem cell or solid organ transplant.
  • Administration of a live, attenuated vaccine within 4 weeks for first study treatment.
  • Pregnant or lactating women.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02724878

Contacts
Contact: Toni Choueiri, MD 617-632-5456 Toni_Choueiri@DFCI.HARVARD.EDU

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02115
Contact: David F McDermott, MD    617-726-1594      
Principal Investigator: David F McDermott, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Toni Choueiri, MD    617-632-5456    Toni_Choueiri@DFCI.HARVARD.EDU   
Principal Investigator: Toni Choueiri, MD         
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Ulka Vaishampayan, MD       vaishamu@karmanos.org   
Principal Investigator: Ulka Vaishampayan, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Genentech, Inc.
Investigators
Principal Investigator: Toni Choueiri, MD Dana-Farber Cancer Institute
  More Information

Responsible Party: Toni Choueiri, MD, Toni K. Choueiri, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02724878     History of Changes
Other Study ID Numbers: 15-592
Study First Received: March 16, 2016
Last Updated: May 2, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Toni Choueiri, MD, Dana-Farber Cancer Institute:
Kidney Cancer

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Bevacizumab
Antibodies, Monoclonal
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 23, 2017