Atezolizumab With Bevacizumab in Previously Untreated Metastatic/Unresectable Urothelial Cancer

NCT03272217 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HCRN GU15-215
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Urothelial Carcinoma

Keywords

Atezolizumab; MPDL3280A; Bevacizumab; Avastin; Cisplatin-Ineligible; Anti-PD-L1 Antibodies

Outcome Measures

Primary Outcomes (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.

  1 years

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Up to a maximum of 14 months

• Duration of Response (DOR)

  Up to a maximum of 14 months

• Progression-Free Survival (PFS)

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

• Number of Participants With Adverse Events

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

Study Arms (1)

Arm A - Atezolizumab + Bevacizumab

EXPERIMENTAL

Patients will receive atezolizumab 1200 mg (flat dose) IV plus bevacizumab 15 mg/kg IV every 21 days

Drug: Atezolizumab; Drug: Bevacizumab

Interventions

Atezolizumab DRUG

Atezolizumab 1200 mg (flat dose) IV every 21 days

Also known as: MPDL3280A

Arm A - Atezolizumab + Bevacizumab

Bevacizumab DRUG

Bevacizumab 15 mg/kg IV every 21 days

Also known as: Avastin

Arm A - Atezolizumab + Bevacizumab

Eligibility Criteria

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

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Arjun Balar, MD: lead
• Roche-Genentech: collaborator
• Hoosier Cancer Research Network: collaborator

Study Sites (8)

University of Arizona at Dignity Health St. Joseph

Phoenix, Arizona, 85004, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

HealthPartners Institute

Minneapolis, Minnesota, 55440, United States

Location

New York University Clinical Cancer Center

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

West Cancer Center University of Tennessee

Memphis, Tennessee, 38120, United States

Location

Froedtert & The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Links

• Hoosier Cancer Research Network Website

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Fauzia Sharmin
• Organization: Hoosier Cancer Research Network

fsharmin@hoosiercancer.org

317-634-5842

Study Officials

• Arjun Balar, M.D.

  Hoosier Cancer Research Network

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open-Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: September 1, 2017
• First Posted: September 5, 2017
• Study Start: September 13, 2017
• Primary Completion: May 27, 2021
• Study Completion: March 17, 2022
• Last Updated: January 7, 2025
• Results First Posted: January 7, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)