A Window of Opportunity Trial: Avelumab in Non-metastatic Muscle Invasive Bladder Cancer
NCT ID: NCT03498196
Last Updated: 2020-08-24
Study Results
Results available
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
TERMINATED
Clinical Phase
PHASE1/PHASE2
Total Enrollment
1 participants
Study Classification
INTERVENTIONAL
Study Start Date
2018-12-14
Study Completion Date
2019-12-09
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
This is a pilot study of avelumab in patients with non-metastatic, muscle invasive bladder cancer who are eligible for radical cystectomy (RC), but are ineligible for cisplatin based neoadjuvant therapy. The target recruitment is 10 evaluable patients for this window of opportunity study. Pre- and post-treatment tumor samples from transurethral resection of the bladder tumor and RC will be used for study endpoints.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Avelumab and Radiation in Muscle-Invasive Bladder Cancer
NCT03747419
Bladder Cancer
Muscle Invasive Bladder Cancer
TERMINATED
PHASE2
Copanlisib and Avelumab as a Maintenance Therapy for Advanced Bladder Cancer
NCT05687721
Advanced Urothelial Carcinoma
WITHDRAWN
PHASE1/PHASE2
A Study Of Avelumab In Patients With Locally Advanced Or Metastatic Urothelial Cancer (JAVELIN Bladder 100)
NCT02603432
Urothelial Cancer
COMPLETED
PHASE3
A Study to Learn About the Study Medicine (Called Avelumab) in People With Advanced Urothelial Cancer After Chemotherapy
NCT05366725
Urothelial Cancer
COMPLETED
Avelumab in Combination With Fluorouracil and Mitomycin or Cisplatin and Radiation Therapy in Treating Participants With Muscle-Invasive Bladder Cancer
NCT03617913
Bladder Carcinoma Infiltrating the Muscle of the Bladder Wall
Stage II Bladder Cancer AJCC v8
Stage II Renal Pelvis Cancer AJCC v8
+9 more
COMPLETED
PHASE2
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Avelumab is a fully human monoclonal PD-L1 antibody of the immunoglobulin G1 (IgG1) subclass. It works by binding to PD-L1 on tumor cells, immune cells and/or stromal cells. This prevents PD-L1 from interacting with PD-1. Inhibition of this interaction increases activation/survival of antitumor lymphocytes. It also increases innate immunity by resulting in decreased PD-1 suppression of NK cell function and bolsters antibody production by B cells due to less PD-L1 binding of PD-1 on B-cells. Additionally, avelumab has been suggested to have another mechanism involving antibody dependent cellular cytotoxicity (ADCC). ADCC in these cases involves NK cell recognition and lysis of tumor cells that have antibody bound to PD-L1. By blocking PD-L1, avelumab leads to less CD80 binding by PD-L1 and more CD80-CD28 binding in response to antigen presentation to T-cells. This results in increased costimulatory signaling and is another mechanism by which avelumab may enhance T-cell activation.
Avelumab has been shown to be efficacious across multiple metastatic tumor types, including urothelial cancer. The phase Ib study has reported survival and safety outcomes with \>12 months followup using pooled data on 249 patients with metastatic UC (Apolo et al, ESMO Sept 2017). Patients had been treated with a median of 2 prior therapies in the metastatic setting and 13 patients who were cisplatin-ineligible were evaluated for safety alone. PD-L1 expression was not a criterion for enrollment. The confirmed objective response rate (ORR) was 16.1%, with 5% complete responses and 11.2% partial responses. The 6-month progression-free survival was 27%. The ORR was better than or comparable to chemotherapy in historical controls. Among responders, 70.3% were maintained \> 12 months. Treatment-related adverse events (AE) occurred in 70%, with 10.7% of the total with AE's of grade \>3. Immune-mediated AE's occurred in 18.5%, of which 4% were grade \>3. There is currently a phase III clinical trial ongoing comparing avelumab to standard of care chemotherapy in the second line setting or beyond for metastatic UC. Two other checkpoint inhibitors have been approved in the last 2 years for first line treatment of patients with metastatic UC who are ineligible for cisplatin-based therapy.
Avelumab has been shown to be efficacious across multiple metastatic tumor types, including urothelial cancer. The phase Ib study has reported survival and safety outcomes with \>12 months followup using pooled data on 249 patients with metastatic UC (Apolo et al, ESMO Sept 2017). Patients had been treated with a median of 2 prior therapies in the metastatic setting and 13 patients who were cisplatin-ineligible were evaluated for safety alone. PD-L1 expression was not a criterion for enrollment. The confirmed objective response rate (ORR) was 16.1%, with 5% complete responses and 11.2% partial responses. The 6-month progression-free survival was 27%. The ORR was better than or comparable to chemotherapy in historical controls. Among responders, 70.3% were maintained \> 12 months. Treatment-related adverse events (AE) occurred in 70%, with 10.7% of the total with AE's of grade \>3. Immune-mediated AE's occurred in 18.5%, of which 4% were grade \>3. There is currently a phase III clinical trial ongoing comparing avelumab to standard of care chemotherapy in the second line setting or beyond for metastatic UC. Two other checkpoint inhibitors have been approved in the last 2 years for first line treatment of patients with metastatic UC who are ineligible for cisplatin-based therapy.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Bladder Cancer
Metastatic Bladder Cancer
Invasive Bladder Cancer
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Allocation Method
NA
Intervention Model
SINGLE_GROUP
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Avelumab
Avelumab 10 mg/kg intravenously, over 60 minutes every 2 weeks for 3 cycles or 42 days.
Group Type
EXPERIMENTAL
Avelumab
Intervention Type
DRUG
avelumab 10 mg/kg intravenously every 2 weeks for 3 cycles or 42 days.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Avelumab
avelumab 10 mg/kg intravenously every 2 weeks for 3 cycles or 42 days.
Intervention Type
DRUG
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
MSB0010718C
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Have undergone TURBT showing newly diagnosed muscle invasive UCB (mixed histology is allowed if the predominant histology is UCC) within 6 weeks prior to cycle 1, day 1 of treatment.
* No prior systemic treatment for muscle invasive UCB
* Clinical T2-T4a disease
* No evidence of clinically positive lymph nodes or distant metastasis on computed tomography (CT) scans of chest and CT or magnetic resonance imaging (MRI) studies of the abdomen/pelvis. Imaging must be within 90 days of registration.
* Male or female subjects aged ≥ 18 years old.
* Must have adequate kidney, liver, and bone marrow function within 30 days of registration, as follows:
* Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
* platelet count ≥ 100 × 109/L
* hemoglobin ≥ 9 g/dL (may have been transfused)
* Total bilirubin level ≤ 1.5 × ULN
* AST and ALT levels ≤ 2.5 × ULN
* Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula
* Negative serum or urine pregnancy test at screening for women of childbearing potential (WOCBP), within 30 days of registration.
* Both male and female subjects must agree to use highly effective contraception (see Section 6.1 Table 8) while receiving avelumab and for at least 60 days after last avelumab treatment if the risk of conception exists.
Female patients must agree to inform study coordinator or investigator immediately if they think they have become pregnant during the study.
* Must have FFPE tissue available from the TURBT, and patient must consent to the use of tissue specimens from TURBT and RC for the study.
* Patients must be ineligible for cisplatin-based NAC. Ineligibility criteria include: creatinine clearance \< 60 ml/min by Cockcroft-Gault formula, CTCAE grade ≥ 2 hearing loss, CTCAE grade ≥ 2 neuropathy, and at discretion of medical oncologist.
* Must be eligible for RC in the opinion of the treating investigator, and willing to undergo this procedure.
* ECOG performance status (PS) score of 0-2
* Signed informed consent form.
* No prior systemic treatment for muscle invasive UCB
* Clinical T2-T4a disease
* No evidence of clinically positive lymph nodes or distant metastasis on computed tomography (CT) scans of chest and CT or magnetic resonance imaging (MRI) studies of the abdomen/pelvis. Imaging must be within 90 days of registration.
* Male or female subjects aged ≥ 18 years old.
* Must have adequate kidney, liver, and bone marrow function within 30 days of registration, as follows:
* Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
* platelet count ≥ 100 × 109/L
* hemoglobin ≥ 9 g/dL (may have been transfused)
* Total bilirubin level ≤ 1.5 × ULN
* AST and ALT levels ≤ 2.5 × ULN
* Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula
* Negative serum or urine pregnancy test at screening for women of childbearing potential (WOCBP), within 30 days of registration.
* Both male and female subjects must agree to use highly effective contraception (see Section 6.1 Table 8) while receiving avelumab and for at least 60 days after last avelumab treatment if the risk of conception exists.
Female patients must agree to inform study coordinator or investigator immediately if they think they have become pregnant during the study.
* Must have FFPE tissue available from the TURBT, and patient must consent to the use of tissue specimens from TURBT and RC for the study.
* Patients must be ineligible for cisplatin-based NAC. Ineligibility criteria include: creatinine clearance \< 60 ml/min by Cockcroft-Gault formula, CTCAE grade ≥ 2 hearing loss, CTCAE grade ≥ 2 neuropathy, and at discretion of medical oncologist.
* Must be eligible for RC in the opinion of the treating investigator, and willing to undergo this procedure.
* ECOG performance status (PS) score of 0-2
* Signed informed consent form.
Exclusion Criteria
Patients must not have any of the following:
* IMMUNOSUPRESSANTS: Current use of immunosuppressive medication or within 4 weeks of C1D1, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
* AUTOIMMUNE DISEASE: Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. Patients with type I diabetes or hypo- or hyperthyroidism should be on stable doses of medications for participation.
* ORGAN TRANSPLANTATION: Prior organ transplantation including allogenic stem-cell transplantation.
* INFECTIONS: Active infection requiring systemic therapy.
* HIV/AIDS: Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
* HEPATITIS: Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
* VACCINATION: Vaccinate within 4 weeks of the first dose of avelumab and while on study drug is prohibited except for administration of inactivated vaccines
* HYPERSENSITIIVTY TO STUDY DRUG: Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)
* CARDIOVASCULAR DISEASE: Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
* Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
* Relapsed MIBC (all patients participating in the study should be newly diagnosed)
* Concomitant UCC outside the bladder (e.g., ureter, urethra or renal pelvis)
* Underlying immune disorder (e.g., combined variable immunodeficiency syndrome)
* Erythropoietin receptor agonists within 30 days prior to enrollment.
* G-CSF, GM-CSF or TPO mimetics during the study period or within 3 weeks prior to study enrollment
* Malignancies other than UCB within 5 years prior to Cycle 1, Day 1, with the exception of those with low risk of metastasis or death treated with expected curative outcome (such as, but not limited to, adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated with curative intent and absence of PSA relapse, or ductal carcinoma in situ of the breast treated surgically with curative intent) or incidental prostate cancer (T1a, Gleason score ≤ 6 and PSA \< 0.5 ng/ml)
* Prior immunotherapy with T-cell co-stimulation or checkpoint targeted agents (e.g., CTLA-4 inhibitors, anti-PD1 antibodies or anti-PD-L1 antibodies)
* Intravesical chemotherapy or biologic therapy within 6 weeks of Cycle 1, Day 1
* Current participation in another clinical trial for MIBC
* Nursing or pregnant woman
* Uncontrolled cystitis, significant bladder pain or spasms, or gross hematuria that in the opinion of the principal investigator will preclude study participation
* Major surgical procedures within 4 weeks of registration (other than for diagnosis) or anticipation that such a procedure will be needed during the study (other than RC)
* IMMUNOSUPRESSANTS: Current use of immunosuppressive medication or within 4 weeks of C1D1, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
* AUTOIMMUNE DISEASE: Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. Patients with type I diabetes or hypo- or hyperthyroidism should be on stable doses of medications for participation.
* ORGAN TRANSPLANTATION: Prior organ transplantation including allogenic stem-cell transplantation.
* INFECTIONS: Active infection requiring systemic therapy.
* HIV/AIDS: Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
* HEPATITIS: Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
* VACCINATION: Vaccinate within 4 weeks of the first dose of avelumab and while on study drug is prohibited except for administration of inactivated vaccines
* HYPERSENSITIIVTY TO STUDY DRUG: Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)
* CARDIOVASCULAR DISEASE: Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
* Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
* Relapsed MIBC (all patients participating in the study should be newly diagnosed)
* Concomitant UCC outside the bladder (e.g., ureter, urethra or renal pelvis)
* Underlying immune disorder (e.g., combined variable immunodeficiency syndrome)
* Erythropoietin receptor agonists within 30 days prior to enrollment.
* G-CSF, GM-CSF or TPO mimetics during the study period or within 3 weeks prior to study enrollment
* Malignancies other than UCB within 5 years prior to Cycle 1, Day 1, with the exception of those with low risk of metastasis or death treated with expected curative outcome (such as, but not limited to, adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated with curative intent and absence of PSA relapse, or ductal carcinoma in situ of the breast treated surgically with curative intent) or incidental prostate cancer (T1a, Gleason score ≤ 6 and PSA \< 0.5 ng/ml)
* Prior immunotherapy with T-cell co-stimulation or checkpoint targeted agents (e.g., CTLA-4 inhibitors, anti-PD1 antibodies or anti-PD-L1 antibodies)
* Intravesical chemotherapy or biologic therapy within 6 weeks of Cycle 1, Day 1
* Current participation in another clinical trial for MIBC
* Nursing or pregnant woman
* Uncontrolled cystitis, significant bladder pain or spasms, or gross hematuria that in the opinion of the principal investigator will preclude study participation
* Major surgical procedures within 4 weeks of registration (other than for diagnosis) or anticipation that such a procedure will be needed during the study (other than RC)
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Pfizer
INDUSTRY
Sponsor Role
collaborator
Baylor College of Medicine
OTHER
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Jennifer Taylor
Assistant Professor of Urology
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Jennifer M. Taylor, MD
Role: PRINCIPAL_INVESTIGATOR
Baylor College of Medicine
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Baylor College of Medicine Medical Center - McNair Campus
Houston, Texas, United States
Site Status
Ben Taub General Hospital
Houston, Texas, United States
Site Status
Michael E. DeBakey Veteran Affairs Medical Center
Houston, Texas, United States
Site Status
Countries
Review the countries where the study has at least one active or historical site.
United States
References
Explore related publications, articles, or registry entries linked to this study.
Fairey AS, Daneshmand S, Quinn D, Dorff T, Dorin R, Lieskovsky G, Schuckman A, Cai J, Miranda G, Skinner EC. Neoadjuvant chemotherapy with gemcitabine/cisplatin vs. methotrexate/vinblastine/doxorubicin/cisplatin for muscle-invasive urothelial carcinoma of the bladder: a retrospective analysis from the University of Southern California. Urol Oncol. 2013 Nov;31(8):1737-43. doi: 10.1016/j.urolonc.2012.07.005. Epub 2012 Nov 7.
Reference Type
BACKGROUND
Galsky MD, Pal SK, Chowdhury S, Harshman LC, Crabb SJ, Wong YN, Yu EY, Powles T, Moshier EL, Ladoire S, Hussain SA, Agarwal N, Vaishampayan UN, Recine F, Berthold D, Necchi A, Theodore C, Milowsky MI, Bellmunt J, Rosenberg JE; Retrospective International Study of Cancers of the Urothelial Tract (RISC) Investigators. Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer. Cancer. 2015 Aug 1;121(15):2586-93. doi: 10.1002/cncr.29387. Epub 2015 Apr 14.
Reference Type
BACKGROUND
Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr, Raghavan D, Crawford ED. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003 Aug 28;349(9):859-66. doi: 10.1056/NEJMoa022148.
Reference Type
BACKGROUND
Herchenhorn D, Dienstmann R, Peixoto FA, de Campos FS, Santos VO, Moreira DM, Cardoso H, Small IA, Ferreira CG. Phase II trial of neoadjuvant gemcitabine and cisplatin in patients with resectable bladder carcinoma. Int Braz J Urol. 2007 Sep-Oct;33(5):630-8; discussion 638. doi: 10.1590/s1677-55382007000500004.
Reference Type
BACKGROUND
International Collaboration of Trialists; Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group); European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group; Australian Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; Finnbladder; Norwegian Bladder Cancer Study Group; Club Urologico Espanol de Tratamiento Oncologico Group; Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011 Jun 1;29(16):2171-7. doi: 10.1200/JCO.2010.32.3139. Epub 2011 Apr 18.
Reference Type
BACKGROUND
Plimack ER, Hoffman-Censits JH, Viterbo R, Trabulsi EJ, Ross EA, Greenberg RE, Chen DY, Lallas CD, Wong YN, Lin J, Kutikov A, Dotan E, Brennan TA, Palma N, Dulaimi E, Mehrazin R, Boorjian SA, Kelly WK, Uzzo RG, Hudes GR. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin is safe, effective, and efficient neoadjuvant treatment for muscle-invasive bladder cancer: results of a multicenter phase II study with molecular correlates of response and toxicity. J Clin Oncol. 2014 Jun 20;32(18):1895-901. doi: 10.1200/JCO.2013.53.2465. Epub 2014 May 12.
Reference Type
BACKGROUND
van de Putte EE, Mertens LS, Meijer RP, van der Heijden MS, Bex A, van der Poel HG, Kerst JM, Bergman AM, Horenblas S, van Rhijn BW. Neoadjuvant induction dose-dense MVAC for muscle invasive bladder cancer: efficacy and safety compared with classic MVAC and gemcitabine/cisplatin. World J Urol. 2016 Feb;34(2):157-62. doi: 10.1007/s00345-015-1636-y. Epub 2015 Jul 17.
Reference Type
BACKGROUND
Winquist E, Kirchner TS, Segal R, Chin J, Lukka H; Genitourinary Cancer Disease Site Group, Cancer Care Ontario Program in Evidence-based Care Practice Guidelines Initiative. Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: a systematic review and meta-analysis. J Urol. 2004 Feb;171(2 Pt 1):561-9. doi: 10.1097/01.ju.0000090967.08622.33.
Reference Type
BACKGROUND
Yeshchina O, Badalato GM, Wosnitzer MS, Hruby G, RoyChoudhury A, Benson MC, Petrylak DP, McKiernan JM. Relative efficacy of perioperative gemcitabine and cisplatin versus methotrexate, vinblastine, adriamycin, and cisplatin in the management of locally advanced urothelial carcinoma of the bladder. Urology. 2012 Feb;79(2):384-90. doi: 10.1016/j.urology.2011.10.050. Epub 2011 Dec 22.
Reference Type
BACKGROUND
Yuh BE, Ruel N, Wilson TG, Vogelzang N, Pal SK. Pooled analysis of clinical outcomes with neoadjuvant cisplatin and gemcitabine chemotherapy for muscle invasive bladder cancer. J Urol. 2013 May;189(5):1682-6. doi: 10.1016/j.juro.2012.10.120. Epub 2012 Nov 1.
Reference Type
BACKGROUND
Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol. 2005 Aug;48(2):202-5; discussion 205-6. doi: 10.1016/j.eururo.2005.04.006. Epub 2005 Apr 21.
Reference Type
BACKGROUND
Bellmunt J, Ribas A, Eres N, Albanell J, Almanza C, Bermejo B, Sole LA, Baselga J. Carboplatin-based versus cisplatin-based chemotherapy in the treatment of surgically incurable advanced bladder carcinoma. Cancer. 1997 Nov 15;80(10):1966-72. doi: 10.1002/(sici)1097-0142(19971115)80:103.0.co;2-w.
Reference Type
BACKGROUND
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012 Mar 22;12(4):252-64. doi: 10.1038/nrc3239.
Reference Type
BACKGROUND
Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Aug 19;363(8):711-23. doi: 10.1056/NEJMoa1003466. Epub 2010 Jun 5.
Reference Type
BACKGROUND
Wolchok JD, Weber JS, Maio M, Neyns B, Harmankaya K, Chin K, Cykowski L, de Pril V, Humphrey R, Lebbe C. Four-year survival rates for patients with metastatic melanoma who received ipilimumab in phase II clinical trials. Ann Oncol. 2013 Aug;24(8):2174-80. doi: 10.1093/annonc/mdt161. Epub 2013 May 10.
Reference Type
BACKGROUND
Liu J, Hamrouni A, Wolowiec D, Coiteux V, Kuliczkowski K, Hetuin D, Saudemont A, Quesnel B. Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-gamma and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway. Blood. 2007 Jul 1;110(1):296-304. doi: 10.1182/blood-2006-10-051482. Epub 2007 Mar 15.
Reference Type
BACKGROUND
Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, Chen S, Klein AP, Pardoll DM, Topalian SL, Chen L. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med. 2012 Mar 28;4(127):127ra37. doi: 10.1126/scitranslmed.3003689.
Reference Type
BACKGROUND
Daud AI, Wolchok JD, Robert C, Hwu WJ, Weber JS, Ribas A, Hodi FS, Joshua AM, Kefford R, Hersey P, Joseph R, Gangadhar TC, Dronca R, Patnaik A, Zarour H, Roach C, Toland G, Lunceford JK, Li XN, Emancipator K, Dolled-Filhart M, Kang SP, Ebbinghaus S, Hamid O. Programmed Death-Ligand 1 Expression and Response to the Anti-Programmed Death 1 Antibody Pembrolizumab in Melanoma. J Clin Oncol. 2016 Dec;34(34):4102-4109. doi: 10.1200/JCO.2016.67.2477. Epub 2016 Oct 31.
Reference Type
BACKGROUND
Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. doi: 10.1056/NEJMoa1606774. Epub 2016 Oct 8.
Reference Type
BACKGROUND
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
BACKGROUND
Huang RY, Eppolito C, Lele S, Shrikant P, Matsuzaki J, Odunsi K. LAG3 and PD1 co-inhibitory molecules collaborate to limit CD8+ T cell signaling and dampen antitumor immunity in a murine ovarian cancer model. Oncotarget. 2015 Sep 29;6(29):27359-77. doi: 10.18632/oncotarget.4751.
Reference Type
BACKGROUND
Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ, Bettini ML, Gravano DM, Vogel P, Liu CL, Tangsombatvisit S, Grosso JF, Netto G, Smeltzer MP, Chaux A, Utz PJ, Workman CJ, Pardoll DM, Korman AJ, Drake CG, Vignali DA. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. 2012 Feb 15;72(4):917-27. doi: 10.1158/0008-5472.CAN-11-1620. Epub 2011 Dec 20.
Reference Type
BACKGROUND
Sweis RF, Spranger S, Bao R, Paner GP, Stadler WM, Steinberg G, Gajewski TF. Molecular Drivers of the Non-T-cell-Inflamed Tumor Microenvironment in Urothelial Bladder Cancer. Cancer Immunol Res. 2016 Jul;4(7):563-8. doi: 10.1158/2326-6066.CIR-15-0274. Epub 2016 May 17.
Reference Type
BACKGROUND
Carthon BC, Wolchok JD, Yuan J, Kamat A, Ng Tang DS, Sun J, Ku G, Troncoso P, Logothetis CJ, Allison JP, Sharma P. Preoperative CTLA-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial. Clin Cancer Res. 2010 May 15;16(10):2861-71. doi: 10.1158/1078-0432.CCR-10-0569. Epub 2010 May 11.
Reference Type
BACKGROUND
Massard C, Gordon MS, Sharma S, Rafii S, Wainberg ZA, Luke J, Curiel TJ, Colon-Otero G, Hamid O, Sanborn RE, O'Donnell PH, Drakaki A, Tan W, Kurland JF, Rebelatto MC, Jin X, Blake-Haskins JA, Gupta A, Segal NH. Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer. J Clin Oncol. 2016 Sep 10;34(26):3119-25. doi: 10.1200/JCO.2016.67.9761. Epub 2016 Jun 6.
Reference Type
BACKGROUND
Sharma P, Callahan MK, Bono P, Kim J, Spiliopoulou P, Calvo E, Pillai RN, Ott PA, de Braud F, Morse M, Le DT, Jaeger D, Chan E, Harbison C, Lin CS, Tschaika M, Azrilevich A, Rosenberg JE. Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial. Lancet Oncol. 2016 Nov;17(11):1590-1598. doi: 10.1016/S1470-2045(16)30496-X. Epub 2016 Oct 9.
Reference Type
BACKGROUND
Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, Vogelzang NJ, Climent MA, Petrylak DP, Choueiri TK, Necchi A, Gerritsen W, Gurney H, Quinn DI, Culine S, Sternberg CN, Mai Y, Poehlein CH, Perini RF, Bajorin DF; KEYNOTE-045 Investigators. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med. 2017 Mar 16;376(11):1015-1026. doi: 10.1056/NEJMoa1613683. Epub 2017 Feb 17.
Reference Type
BACKGROUND
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
BACKGROUND
Oing C, Rink M, Oechsle K, Seidel C, von Amsberg G, Bokemeyer C. Second Line Chemotherapy for Advanced and Metastatic Urothelial Carcinoma: Vinflunine and Beyond-A Comprehensive Review of the Current Literature. J Urol. 2016 Feb;195(2):254-63. doi: 10.1016/j.juro.2015.06.115. Epub 2015 Sep 26.
Reference Type
BACKGROUND
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
Access external resources that provide additional context or updates about the study.
http://www.ascopost.com/News/44121
SITC 2016: Immune Checkpoint Inhibitors Shrink Tumors in Some Patients With Metastatic Bladder Cancer
http://www.ascopost.com/issues/december-10-2016/cardiac-complications-in-patients-receiving-combination-checkpoint-inhibitors-are-rare-but-can-be-fatal/
Cardiac Complications in Patients Receiving Combination Checkpoint Inhibitors Are Rare but Can Be Fatal
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
H-41207
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.
Adjuvant Nivolumab Following Chemo-Radiation in Localized Muscle-Invasive Bladder Cancer
NCT03171025
ACTIVE_NOT_RECRUITING
PHASE2
A NON-INTERVENTIONAL STUDY ON AVELUMAB USE IN PATIENTS WITH ADVANCED OR METASTATIC UROTHELIAL CARCINOMA
NCT04822350
COMPLETED
A Study of Nivolumab Intravenous (IV) to Subcutaneous (SC) Switch in Adjuvant Melanoma and Bladder Cancer
NCT05496192
WITHDRAWN
PHASE2
A Study to Learn About the Effect of Avelumab First-Line Maintenance in Canadian People With Advanced Bladder Cancer
NCT05699135
TERMINATED
Cryoablation With Pembrolizumab Or Avelumab In Urothelial Carcinoma
NCT04701918
COMPLETED
PHASE2
Neoadjuvant Nivolumab With and Without Urelumab in Cisplatin-Ineligible or Chemotherapy-refusing Patients With Muscle-Invasive Urothelial Carcinoma of the Bladder
NCT02845323
ACTIVE_NOT_RECRUITING
PHASE2
First-line Gemcitabine/Cisplatin +/- Avelumab in Locally Advanced or Metastatic Bladder Carcinoma
NCT03324282
TERMINATED
PHASE2
Nivolumab and RT in Treating Patients With Localized/Locally Advanced Urothelial Bladder Cancer Ineligible for Chemo
NCT03421652
COMPLETED
PHASE2
Avelumab Plus Bacille Calmette-Guerin (BCG) in Patients With Non-muscle Invasive Bladder Cancer
NCT03892642
COMPLETED
PHASE1/PHASE2
Tetra-modality Bladder Preservation Strategies in Muscle-invasive Bladder Cancer: TURBT+ Chemo/Immunotherapy+ Radiation Therapy+ Maintenance Immunotherapy vs. W&W
NCT06686381
NOT_YET_RECRUITING
PHASE2
Window of Opportunity Study of Pembrolizumab Alone and in Combinations in Bladder Cancer
NCT03978624
ACTIVE_NOT_RECRUITING
PHASE2
A Study of the Safety and Efficacy of Various Combinations of Avelumab as Therapy in Locally Advanced or Metastatic Urothelial Carcinoma (JAVELIN Bladder Medley)
NCT05327530
ACTIVE_NOT_RECRUITING
PHASE2
Avelumab as Neoadjuvant Therapy in Subjects With Urothelial Muscle Invasive Bladder Cancers (AURA Trial)
NCT03674424
COMPLETED
PHASE2
Atezolizumab With Bevacizumab in Previously Untreated Metastatic/Unresectable Urothelial Cancer
NCT03272217
TERMINATED
PHASE2
Erlotinib Hydrochloride in Treating Participants With Muscle Invasive or Recurrent Urothelial Cancer
NCT00749892
COMPLETED
PHASE2
Study of Avelumab and Tuvusertib in Participants With Advanced Urothelial Cancer That Has Progressed on Prior Anti-PD-(L)1 Therapy (JAVELIN DDRiver Bladder)
NCT06424717
WITHDRAWN
PHASE2
A Study of Nivolumab in Participants With Metastatic or Unresectable Bladder Cancer
NCT02387996
COMPLETED
PHASE2
Testing the Addition of an Anti-Cancer Immunotherapy Drug, Avelumab, to Gemcitabine and Carboplatin Chemotherapy Prior to Surgery in Muscle Invasive Urinary Tract Cancer vs. Surgery Alone in Patients Who Are Not Able to Receive Cisplatin Therapy (SWOG GAP TRIAL)
NCT04871529
TERMINATED
PHASE2
KHK2455 (IDO Inhibitor) Plus Avelumab in Adult Subjects With Advanced Bladder Cancer
NCT03915405
TERMINATED
PHASE1
Drug Screening Using IMD in Bladder Cancer
NCT06204614
NOT_YET_RECRUITING
EARLY_PHASE1
Testing MK-3475 (Pembrolizumab) After Surgery for Localized Muscle-Invasive Bladder Cancer and Locally Advanced Urothelial Cancer
NCT03244384
ACTIVE_NOT_RECRUITING
PHASE3
A Combination of Avelumab and Taxane (AVETAX) for Urothelial Cancer
NCT03575013
COMPLETED
PHASE1
Erlotinib Hydrochloride in Treating Patients With Bladder Cancer Undergoing Surgery
NCT02169284
TERMINATED
PHASE2