A Study of Atezolizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer (Cohort 2)

NCT ID: NCT02108652

Last Updated: 2024-03-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 310 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2023-02-28

Brief Summary

This Phase II, single-arm study is designed to evaluate the effect of atezolizumab treatment in participants with locally advanced or metastatic urothelial bladder cancer. Participants will be enrolled into 1 of 2 cohorts. Cohort 1 will consist of participants who are treatment-naïve and ineligible for cisplatin-containing chemotherapy. The results of Cohort 1 are reported separately (NCT02951767). Cohort 2 (reported here) will contain participants who have progressed during or following a prior platinum-based chemotherapy regimen. Participants in both cohorts will be given a 1200 milligrams (mg) intravenous (IV) dose of atezolizumab on Day 1 of 21-day cycles. Treatment of participants in Cohort 1 will continue until disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or unmanageable toxicity. Treatment of participants in Cohort 2 will continue until loss of clinical benefit or unmanageable toxicity.

Conditions

Bladder Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 2: Participants With Second-line or Beyond Treatments

Participants with advanced disease who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting will receive atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab 1200 mg given by IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria/loss of clinical benefit or unmanageable toxicity.

Interventions

Atezolizumab

Atezolizumab 1200 mg given by IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria/loss of clinical benefit or unmanageable toxicity.

Intervention Type: DRUG

Other Intervention Names

MPDL3280A; Tecentriq

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, urethra)
• Representative tumor specimens as specified by the protocol
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy greater than or equal to (>=) 12 weeks
• Measurable disease, as defined by RECIST v1.1
• Adequate hematologic and end organ function

• Disease progression during or following treatment with at least one platinum-containing regimen (e.g., gemcitabine and cisplatin [GC], methotrexate, vinblastine, doxorubicin, and cisplatin [MVAC], CarboGem, etc.) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence.
• A regimen was defined as participants receiving at least two cycles of a platinum-containing regimen. Participants who had received one cycle of a platinum-containing regimen but discontinued due to Grade 4 hematologic toxicity or Grade 3 or 4 non-hematologic toxicity could also be eligible.
• Participants who received prior adjuvant/neoadjuvant chemotherapy and progressed within 12 months of treatment with a platinum-containing adjuvant/neoadjuvant regimen were considered as second-line participants.

Exclusion Criteria

• Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment
• 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 as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
• Leptomeningeal disease
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Uncontrolled hypercalcemia (greater than [>] 1.5 millimoles per liter [mmol/L] ionized calcium or Ca > 12 milligrams per deciliter [mg/dL] or corrected serum calcium > upper limits of normal [ULN]) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
• Malignancies other than urothelial bladder 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 or incidental prostate cancer
• Pregnant and lactating women
• History of autoimmune disease
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• Serum albumin less than (<) 2.5 grams per deciliter (g/dL)
• Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or hepatitis C or tuberculosis
• Severe infections within 4 weeks prior to Cycle 1, Day 1
• Significant cardiovascular disease
• Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1
• Prior allogeneic stem cell or solid organ transplant
• Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
• 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 patient at high risk from treatment complications
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4), anti-programmed death-1 receptor (anti-PD-1), and anti-programmed death-ligand 1 (anti-PD-L1) therapeutic antibodies

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

University of Alabama At Birmingham

Birmingham, Alabama, United States

Pinnacle Oncology Hematology

Scottsdale, Arizona, United States

Arizona Oncology - HOPE Wilmot

Tucson, Arizona, United States

UCLA

Los Angeles, California, United States

The Angeles Clinic and Research Institute - W LA Office

Los Angeles, California, United States

USC Norris Cancer Center

Los Angeles, California, United States

UCSF

San Francisco, California, United States

Kaiser Permanente - San Marcos

San Marcos, California, United States

Stanford Cancer Center

Stanford, California, United States

Kaiser Permanente; Oncology Clinical Trials

Vallejo, California, United States

Rocky Mountain Cancer Center - Aurora

Aurora, Colorado, United States

University Of Colorado

Aurora, Colorado, United States

University of Connecticut Health Center

Farmington, Connecticut, United States

Yale Cancer Center ; Medical Oncology

New Haven, Connecticut, United States

Georgetown University Medical Center Lombardi Cancer Center

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

Mayo Clinic Cancer Center

Jacksonville, Florida, United States

Piedmont Cancer Institute, PC

Atlanta, Georgia, United States

University of Chicago; Hematology/Oncology

Chicago, Illinois, United States

Ingalls Memorial Hospital

Harvey, Illinois, United States

Indiana University Health; Goshen Center for Cancer Care

Goshen, Indiana, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Massachusetts General Hospital;Oncology

Boston, Massachusetts, United States

Dana Farber Cancer Inst. ; Dept. of Medical Oncology

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center, Harvard Medical School; Department of Medicine

Boston, Massachusetts, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Minnesota Oncology Minneapolis

Minneapolis, Minnesota, United States

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Urology Cancer Center & GU Research Network

Omaha, Nebraska, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

New York Oncology Hematology, P.C.

Albany, New York, United States

NYU Langone Medical Center

New York, New York, United States

Mount Sinai School of Medicine - Tisch Cancer Institute

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Oncology Hematology Care Inc

Cincinnati, Ohio, United States

Case Western Reserve Univ; Hem/Onc

Cleveland, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Willamette Valley Cancer Ctr - 520 Country Club

Eugene, Oregon, United States

Kimmel Cancer Center Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Sarah Cannon Cancer Center - Tennessee Oncology, Pllc

Nashville, Tennessee, United States

Ctr for Cancer and Blood Disorders

Fort Worth, Texas, United States

Texas Oncology - Houston (Gessner)

Houston, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Virginia Oncology Associates - Lake Wright Cancer Center

Norfolk, Virginia, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Bcca - Cancer Center Southern Interior

Kelowna, British Columbia, Canada

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Lakeridge Health Oshawa; Oncology

Oshawa, Ontario, Canada

The Ottawa Hospital Cancer Centre; Oncology

Ottawa, Ontario, Canada

Sunnybrook Odette Cancer Centre

Toronto, Ontario, Canada

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, Canada

McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology

Montreal, Quebec, Canada

APHP - Hospital Saint Louis

Paris, , France

Hopital Foch; Oncologie

Suresnes, , France

Institut Gustave Roussy; Oncologie Medicale

Villejuif, , France

Charité - Universitätsmedizin Berlin; CC 8: Chirurgische Medizin; Klinik für Urologie

Berlin, , Germany

Universitätsklinikum Düsseldorf; Urologische Klinik

Düsseldorf, , Germany

Universitätsklinikum Freiburg; Chirurgische Klinik; Abteilung Urologie

Freiburg im Breisgau, , Germany

Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II

Hamburg, , Germany

Klinikum rechts der Isar der TU München; Urologische Klinik und Poliklinik

München, , Germany

Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2

Milan, Lombardy, Italy

Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia

Arezzo, Tuscany, Italy

The Netherlands Cancer Institute - Antoni Van Leeuwenhoekziekenhuis

Amsterdam, , Netherlands

Clinica Universitaria de Navarra; Servicio de Oncologia

Pamplona, Navarre, Spain

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, , Spain

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, , Spain

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, , Spain

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, , Spain

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, , Spain

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

Seville, , Spain

University Hospital Birmingham The Cancer Centre, Queen Elizabeth Hospital

Birmingham, , United Kingdom

Barts and The London

London, , United Kingdom

Sarah Cannon Research Institute

London, , United Kingdom

The Clatterbridge Cancer Centre NHS Foundation Trust

Metropolitan Borough of Wirral, , United Kingdom

Royal Marsden Hospital; Dept of Medical Oncology

Sutton, , United Kingdom

Countries

United States; Canada; France; Germany; Italy; Netherlands; Spain; United Kingdom

References

Holm JS, Funt SA, Borch A, Munk KK, Bjerregaard AM, Reading JL, Maher C, Regazzi A, Wong P, Al-Ahmadie H, Iyer G, Tamhane T, Bentzen AK, Herschend NO, De Wolf S, Snyder A, Merghoub T, Wolchok JD, Nielsen M, Rosenberg JE, Bajorin DF, Hadrup SR. Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma. Nat Commun. 2022 Apr 11;13(1):1935. doi: 10.1038/s41467-022-29342-0.

Reference Type: DERIVED

PMID: 35410325 (View on PubMed)

Shemesh CS, Chan P, Legrand FA, Shames DS, Das Thakur M, Shi J, Bailey L, Vadhavkar S, He X, Zhang W, Bruno R. Pan-cancer population pharmacokinetics and exposure-safety and -efficacy analyses of atezolizumab in patients with high tumor mutational burden. Pharmacol Res Perspect. 2020 Dec;8(6):e00685. doi: 10.1002/prp2.685.

Reference Type: DERIVED

PMID: 33241650 (View on PubMed)

Teo MY, Seier K, Ostrovnaya I, Regazzi AM, Kania BE, Moran MM, Cipolla CK, Bluth MJ, Chaim J, Al-Ahmadie H, Snyder A, Carlo MI, Solit DB, Berger MF, Funt S, Wolchok JD, Iyer G, Bajorin DF, Callahan MK, Rosenberg JE. Alterations in DNA Damage Response and Repair Genes as Potential Marker of Clinical Benefit From PD-1/PD-L1 Blockade in Advanced Urothelial Cancers. J Clin Oncol. 2018 Jun 10;36(17):1685-1694. doi: 10.1200/JCO.2017.75.7740. Epub 2018 Feb 28.

Reference Type: DERIVED

PMID: 29489427 (View on PubMed)

Perez-Gracia JL, Loriot Y, Rosenberg JE, Powles T, Necchi A, Hussain SA, Morales-Barrera R, Retz MM, Niegisch G, Duran I, Theodore C, Grande E, Shen X, Wang J, Nelson B, Derleth CL, van der Heijden MS. Atezolizumab in Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: Outcomes by Prior Number of Regimens. Eur Urol. 2018 Mar;73(3):462-468. doi: 10.1016/j.eururo.2017.11.023. Epub 2017 Dec 20.

Reference Type: DERIVED

PMID: 29273410 (View on PubMed)

Necchi A, Joseph RW, Loriot Y, Hoffman-Censits J, Perez-Gracia JL, Petrylak DP, Derleth CL, Tayama D, Zhu Q, Ding B, Kaiser C, Rosenberg JE. Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study. Ann Oncol. 2017 Dec 1;28(12):3044-3050. doi: 10.1093/annonc/mdx518.

Reference Type: DERIVED

PMID: 28950298 (View on PubMed)

Snyder A, Nathanson T, Funt SA, Ahuja A, Buros Novik J, Hellmann MD, Chang E, Aksoy BA, Al-Ahmadie H, Yusko E, Vignali M, Benzeno S, Boyd M, Moran M, Iyer G, Robins HS, Mardis ER, Merghoub T, Hammerbacher J, Rosenberg JE, Bajorin DF. Contribution of systemic and somatic factors to clinical response and resistance to PD-L1 blockade in urothelial cancer: An exploratory multi-omic analysis. PLoS Med. 2017 May 26;14(5):e1002309. doi: 10.1371/journal.pmed.1002309. eCollection 2017 May.

Reference Type: DERIVED

PMID: 28552987 (View on PubMed)

Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, Loriot Y, Necchi A, Hoffman-Censits J, Perez-Gracia JL, Dawson NA, van der Heijden MS, Dreicer R, Srinivas S, Retz MM, Joseph RW, Drakaki A, Vaishampayan UN, Sridhar SS, Quinn DI, Duran I, Shaffer DR, Eigl BJ, Grivas PD, Yu EY, Li S, Kadel EE 3rd, Boyd Z, Bourgon R, Hegde PS, Mariathasan S, Thastrom A, Abidoye OO, Fine GD, Bajorin DF; IMvigor210 Study Group. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017 Jan 7;389(10064):67-76. doi: 10.1016/S0140-6736(16)32455-2. Epub 2016 Dec 8.

Reference Type: DERIVED

PMID: 27939400 (View on PubMed)

Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016 May 7;387(10031):1909-20. doi: 10.1016/S0140-6736(16)00561-4. Epub 2016 Mar 4.

Reference Type: DERIVED

PMID: 26952546 (View on PubMed)

Other Identifiers

IMvigor 210

Identifier Type: OTHER

Identifier Source: secondary_id

2013-005486-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO29293 (Cohort 2)

Identifier Type: -

Identifier Source: org_study_id