AzTrials
AzTrials

Urothelial CarcinomaPhase 2NCT03272217

Atezolizumab With Bevacizumab in Previously Untreated Metastatic/Unresectable Urothelial Cancer

A Phase 2 study testing Atezolizumab and Bevacizumab in people with Urothelial Carcinoma, run by Arjun Balar, MD at 8 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This is a phase II study assessing the activity of bevacizumab combined with atezolizumab in metastatic urothelial carcinoma patients who are ineligible for cisplatin-based therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urothelial Carcinoma
What is being tested?
Atezolizumab and Bevacizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
8 sitesUnited States
Study dates
13 Sep 2017to 17 Mar 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient must meet all of the following applicable inclusion criteria to participate in this study:
  • Written informed consent and Health Insurance Portability and Accountability Act of 1996 (HIPAA) authorization for release of personal health information.
  • As determined by the enrolling physician or protocol designee, ability of the patient to understand and comply with study procedures for the entire length of the study
  • Age ≥ 18 years at the time of consent
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2 within 28 days prior to registration
  • Histological or cytological evidence urothelial (transitional cell) carcinoma of the renal pelvis, ureter, bladder or urethra
Show all 23Show fewer
  • Locally advanced/unresectable disease as determined by site attending urologic oncologist or metastatic disease
  • Evaluable untreated tumor tissue for biomarker analysis. Untreated tumor tissue is defined as no intervening intravesical or systemic therapy since acquisition. Patients without tissue available must be willing and safe to undergo biopsy repeat biopsy (core needle or excisional) prior to enrollment. Subjects with < 25 slides may be enrolled after discussion with the sponsor-investigator or co-investigator.
  • Willing to undergo a core needle or excisional biopsy on-treatment. Patients will be assessed at the time of biopsy for safety of undergoing the procedure
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 within 28 days prior to registration
  • No prior chemotherapy for locally advanced or metastatic urothelial cancer
  • Perioperative chemotherapy previously administered in the neoadjuvant and/or adjuvant setting is permitted
  • Prior chemotherapy administered in the context of chemoradiation as definitive treatment for bladder preservation is also permitted, provided that disease progression outside the prior radiotherapy field is demonstrated histologically or cytologically
  • Ineligible for cisplatin as defined by presence of one or more of the following:
  • (Impaired renal function [≤ 60 cc/min]. Glomerular filtration rate (GFR) should be assessed by direct measurement [i.e., creatinine clearance or ethylenediaminetetra-acetate] or, if not available, by calculation from serum/plasma creatinine by Cockroft-Gault equation)
  • Grade ≥ 2 hearing Loss (measured by loss of >25 dB at two contiguous frequencies in at least one ear for patients undergoing serial audiometry testing)
  • Grade ≥ 2 peripheral neuropathy
  • ECOG Performance Status of 2
  • Solitary Kidney
  • Refusing Cisplatin-based chemotherapy
  • If palliative radiotherapy administered, completion of palliative radiation therapy ≥ 2 weeks prior to Cycle 1 Day 1 of protocol therapy
  • Females of childbearing potential must have a negative serum pregnancy test within 28 days prior to registration.
  • Females of childbearing potential and males must be willing to abstain from heterosexual intercourse or to use 2 forms of effective methods of contraception from the time of informed consent until 150 days (5 months) after discontinuation of atezolizumab or 180 days (6 months) after discontinuation of bevacizumab. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method

Who cannot join

  • Patients meeting any of the criteria below may not participate in the study:
  • Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment; the following exceptions are allowed:
  • Palliative radiotherapy for bone metastases or soft tissue lesions should be completed > 7 days prior to baseline imaging
  • Hormone-replacement therapy or oral contraceptives
  • Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
  • Active or untreated central nervous system (CNS) metastases or leptomeningeal disease as determined by computed tomography (CT) scan or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments.
Show all 71Show fewer
  • Patients with treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria:
  • Evaluable or measurable disease outside the CNS
  • No metastases to midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)
  • No history of intracranial or spinal cord hemorrhage
  • No evidence of significant vasogenic edema
  • No ongoing requirement for dexamethasone as therapy for CNS disease; anticonvulsants at a stable dose allowed
  • No stereotactic radiation, whole-brain radiation within 4 weeks prior to Cycle 1 Day 1
  • Patients with central nervous system (CNS) metastases treated by neurosurgical resection or brain biopsy within 3 months prior to Cycle 1 Day 1 will be excluded
  • Radiographic demonstration of interim stability (i.e., no progression) between the completion of CNS-directed therapy and the screening radiographic study
  • Screening CNS radiographic study ≥ 4 weeks since completion of radiotherapy or surgical resection and ≥ 2 weeks since discontinuation of corticosteroids
  • Leptomeningeal disease
  • Uncontrolled tumor-related pain
  • Patients requiring pain medication must be on a stable regimen at study entry
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
  • Patients with indwelling drainage catheters are allowed.
  • Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab. NOTE: Patients with asymptomatic hypercalcemia controlled with medical therapy are eligible.
  • Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible.
  • Patients who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead while in the study.
  • Malignancies other than urothelial cancer within 5 years prior to Cycle 1 Day 1, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (T1/T2a, Gleason score ≤ 3 + 4, and PSA ≤ 0.5 ng/mL undergoing active surveillance and treatment naive)
  • Pregnant or breastfeeding
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab or bevacizumab formulation
  • History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
  • Subjects with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
  • Subjects with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
  • Subjects with a history of celiac disease may be eligible if controlled with diet.
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
  • History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • History of confirmed positive test for human immunodeficiency virus (HIV)
  • Patients with active hepatitis B virus (HBV) (chronic or acute, defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C virus (HCV)
  • Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBc Ab] and absence of HBsAg) are eligible
  • Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA
  • Active tuberculosis
  • Severe infections within 4 weeks prior to Cycle 1 Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Signs or symptoms of active infection within 2 weeks prior to C1D1
  • Received therapeutic oral or IV antibiotics within 1 week prior to C1D1
  • Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible
  • New York Heart Association Congestive Heart Failure Class II or greater
  • Myocardial infarction, unstable angina or unstable arrhythmias within 3 months of enrollment.
  • History of stroke or TIA within 3 months of enrollment
  • Other clinically significant arterial vascular disease within 6 months of enrollment (e.g. aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis). Prior history of adequately treated venous thromboembolism > 7 days prior to C1D1 on stable dose of therapeutic anticoagulation is permitted
  • 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 medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
  • Major surgical procedure other than for diagnosis within 28 days prior to C1D1 or anticipation of need for a major surgical procedure during the course of the study
  • Prior allogeneic stem cell or solid organ transplant
  • Administration of a live, attenuated vaccine within 4 weeks before C1D1 or anticipation that such a live attenuated vaccine will be required during the study
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications
  • ATEZOLIZUMAB-SPECIFIC EXCLUSION CRITERIA:
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  • Prior cancer vaccines and cellular immunotherapy are permitted.
  • Treatment with systemic immunostimulatory agents (including but not limited to IFNs, interleukin [IL]-2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to C1D1
  • Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to C1D1, or anticipated requirement for systemic immunosuppressive medications during the trial
  • 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, physiologic replacement doses of glucocorticoids (i.e., for adrenal insufficiency), and mineralocorticoids (e.g., fludrocortisone for adrenal insufficiency) is allowed
  • BEVACIZUMAB-SPECIFIC EXCLUSION CRITERIA:
  • Inadequately controlled hypertension (defined as persistent systolic blood pressure (SBP) > 150 and/or diastolic blood pressure (DBP) > 100 mmHg)
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
  • Current or recent (within 10 days of study enrollment) use of aspirin (> 325 mg/day), clopidogrel (> 75 mg/day), or current or recent (within 10 days prior to first dose of bevacizumab) use of therapeutic oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes
  • History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month of study enrollment
  • Minor surgical procedure within 7 calendar days prior to C1D1
  • History of abdominal or tracheoesophageal fistula or gastrointestinal perforation within 6 months prior to enrollment
  • Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
  • Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
  • Serious non-healing or dehiscing wound, active ulcer, or untreated or non-healing bone fracture
  • On-going gross hematuria associated with clots

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • West Cancer Center University of Tennessee

    Memphis, Tennessee, 38120

  • Froedtert & The Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • HealthPartners Institute

    Minneapolis, Minnesota, 55440

  • New York University Clinical Cancer Center

    New York, New York, 10016

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Arizona at Dignity Health St. Joseph

    Phoenix, Arizona, 85004

Other trials in United States

About this study

Official title: A Phase II Trial of Atezolizumab and Bevacizumab in Cisplatin-ineligible Patients With Advanced/Unresectable Urothelial Cancer

This is a phase II study assessing the activity of bevacizumab combined with atezolizumab in metastatic urothelial carcinoma patients who are ineligible for cisplatin-based therapy.

Read the detailed description

This is a multi-center trial.

INVESTIGATIONAL TREATMENT:

Eligible patients will be receive atezolizumab 1200 mg IV flat dose plus bevacizumab 15 mg/kg IV every 21 days

21 days equals 1 cycle of therapy and patients will be eligible to continue treatment until progressive disease by RECIST v1.1 or unacceptable toxicity for up to 24 months.

To demonstrate adequate organ function, all screening labs must be obtained within 14 days prior to Cycle 1 Day 1 (C1D1) of treatment:

Hematological:

  • Absolute Neutrophil Count (ANC): ≥ 1,000 K/mm^3
  • Hemoglobin (Hgb): ≥ 9.0 g/dL
  • Absolute Lymphocyte Count: ≥ 500/uL
  • Platelet Count: ≥ 100,000/uL

Renal:

  • Calculated Creatinine Clearance: serum creatinine < 2.5 or ≥ 25 cc/min using a direct method or the Cockcroft-Gault formula
  • Urinary Protein Excretion: < 1.0 g/24 hours (as estimated by urine protein-creatinine ratio)

Hepatic:

  • Bilirubin: ≤ 1.5 × upper limit of normal (ULN) (patients with known Gilbert's Disease who have serum bilirubin ≤ 3.0 x ULN may be enrolled)
  • Aspartate aminotransferase (AST): ≤ 2.5 × ULN (5.0 x ULN if liver involvement)
  • Alanine aminotransferase (ALT): ≤ 2.5 × ULN (5.0 x ULN if liver involvement)
  • Serum Albumin: ≥ 2.5 g/dL

Coagulation:

  • International Normalized Ratio (INR) or Prothrombin Time (PT); Activated Partial Thromboplastin Time (aPTT): ≤ 1.5 × ULN (NOTE: This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose)
Keywords
Atezolizumab, MPDL3280A, Bevacizumab, Avastin, Cisplatin-Ineligible, Anti-PD-L1 Antibodies
Medical subject headings
Carcinoma, Transitional Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called MPDL3280A

    Atezolizumab 1200 mg (flat dose) IV every 21 days

  • BevacizumabDrug

    Also called Avastin

    Bevacizumab 15 mg/kg IV every 21 days

Study groups in NCT03272217
Study groupRoleWhat they receive
Arm A - Atezolizumab + BevacizumabExperimentalPatients will receive atezolizumab 1200 mg (flat dose) IV plus bevacizumab 15 mg/kg IV every 21 days
Receives: Drug: Atezolizumab; Drug: Bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival (OS) Rate at 1 Year

    Determine the percentage of overall survival at 1 years from the initiation of treatment. Overall survival is defined as the time from treatment start until death or date of last contact.

    Measured: 1 years

Secondary outcomes (4)

  1. Objective Response Rate (ORR)

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter(LD) of target lesions; Progressive Disease (PD): >= 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

    Overall Response (OR) = CR + PR.

    Measured: Up to a maximum of 14 months

  2. Duration of Response (DOR)

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD.

    DOR is defined as time from measurement criteria are met for complete or partial response (whichever status is recorded first) until the date that recurrent or progressive disease is objectively documented by RECIST v1.1.

    Measured: Up to a maximum of 14 months

  3. Progression-Free Survival (PFS)

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD.

    PFS is defined as time from the date of treatment start until the criteria for disease progression is met as defined by RECIST 1.1 or death occurs

    Measured: Time of treatment start until the criteria for disease progression or death, up to a maximum of 36 months.

  4. Number of Participants With Adverse Events

    Adverse events were recorded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.

    Measured: Adverse events were recorded from time of registration until 30 days after discontinuation of study drug(s), up to maximum of 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Sep 2017
  2. Study start13 Sep 2017
  3. Primary completion27 May 2021
  4. Study completion17 Mar 2022

Why it stopped: Funder decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03272217
Sponsor's protocol ID
HCRN GU15-215
Status last verified
Dec 2024
First submitted
1 Sep 2017
Last updated
7 Jan 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab and Bevacizumab in people with Urothelial Carcinoma, run by Arjun Balar, MD at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 71 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) Rate at 1 Year (time frame: 1 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03272217.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in