Bladder CancerPhase 1/2NCT03498196
A Window of Opportunity Trial: Avelumab in Non-metastatic Muscle Invasive Bladder Cancer
A Phase 1/2 study testing Avelumab in people with Bladder Cancer and Metastatic Bladder Cancer, run by Baylor College of Medicine at 3 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer, Metastatic Bladder Cancer, Invasive Bladder Cancer
- What is being tested?
- Avelumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 3 sitesUnited States
- Study dates
- 14 Dec 2018to 9 Dec 2019
- Phase
- Phase 1/2
- 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
- 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:
Show all 20Show fewer
- 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.
Who cannot join
- 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.
Show all 23Show fewer
- 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)
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Baylor College of Medicine Medical Center - McNair Campus
Houston, Texas, 77030
Ben Taub General Hospital
Houston, Texas, 77030
Michael E. DeBakey Veteran Affairs Medical Center
Houston, Texas, 77030
About this study
Official title: A Window of Opportunity Trial: Avelumab in Non-metastatic Muscle Invasive Bladder Cancer (BL-AIR: Bladder Cancer-Avelumab for Invasive Resectable Disease)
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.
Read the detailed description
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.
- Being tested
- Avelumab
- Keywords
- muscle invasive bladder cancer, non-muscle invasive bladder cancer, radical cystectomy, monoclonal antibodies, Avelumab, Invasive Resectable disease, MIBC, NMIBC, neoadjuvant chemotherapy
- Medical subject headings
- Urinary Bladder Neoplasms, Non-Muscle Invasive Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvelumabDrug
Also called MSB0010718C
avelumab 10 mg/kg intravenously every 2 weeks for 3 cycles or 42 days.
| Study group | Role | What they receive |
|---|---|---|
| Avelumab | Experimental | Avelumab 10 mg/kg intravenously, over 60 minutes every 2 weeks for 3 cycles or 42 days. Receives: Drug: Avelumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in T Cell Subpopulations
The change in T cell subpopulations (CD8, CD4 and/or CD3) in tumor samples will be collected from FFPE tissue. FFPE tissue from the pre-study time point refers to tissue from the TURBT. FFPE tissue from the 2-3 week post-op time point refers to FFPE tissue from the RC
Measured: pre-study time and 2-3 week post-operation
Secondary outcomes (3)
Pathological Response Rate
Number of patient with pathological response will be counted
Measured: pre-study time and 2-3 week post-operation
2 Year Disease Free Survival (DFS)
A patient will be followed for recurrence and survival for up to 2 years after radical cystectomy.
Measured: 2 years after radical cystectomy
Rate of High Grade(Grade 3-4) Adverse Event
High grade adverse events are defined as grade of 3-4 on the CTCAE (Common terminology criteria for adverse events) grading scale.
Measured: 90 days post operation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2018
- Study start14 Dec 2018
- Primary completion9 Dec 2019
- Study completion9 Dec 2019
Why it stopped: The sponsor of this study has terminated the study due to poor enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (29)Papers the sponsor has linked to this study.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Principal investigator, Jennifer Taylor, Baylor College of Medicine
- Investigators
- Jennifer M. Taylor, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03498196
- Sponsor's protocol ID
- H-41207
- Status last verified
- Aug 2020
- First submitted
- 7 Apr 2018
- Last updated
- 24 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 23141776Galsky 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.
PubMed 25872978Grossman 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.
PubMed 12944571Herchenhorn 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.
PubMed 17980060International 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.
PubMed 21502557Plimack 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.
PubMed 24821881van 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.
PubMed 26184106Winquist 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.
PubMed 14713760Yeshchina 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.
PubMed 22196406Yuh 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.
PubMed 23123547Advanced 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.
PubMed 15939524Bellmunt 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.
PubMed 9366300Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012 Mar 22;12(4):252-64. doi: 10.1038/nrc3239.
PubMed 22437870Hodi 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.
PubMed 20525992Wolchok 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.
PubMed 23666915
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Window of Opportunity Trial: Avelumab in Non-metastatic Muscle Invasive Bladder Cancer (BL-AIR: Bladder Cancer-Avelumab for Invasive Resectable Disease)
- ClinicalTrials.gov ID
- NCT03498196
- Acronym / sponsor ID
- H-41207
- Keywords
- muscle invasive bladder cancer, non-muscle invasive bladder cancer, radical cystectomy, monoclonal antibodies, Avelumab, Invasive Resectable disease, MIBC, NMIBC
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The sponsor of this study has terminated the study due to poor enrollment.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 14 Dec 2018 (actual)
- Primary completion
- 9 Dec 2019 (actual)
- Study completion
- 9 Dec 2019 (actual)
- First posted
- 13 Apr 2018 (actual)
- Results
- Posted 24 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Avelumab | Experimental | Drug: AvelumabAvelumab 10 mg/kg intravenously, over 60 minutes every 2 weeks for 3 cycles or 42 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AvelumabAlso: MSB0010718Cavelumab 10 mg/kg intravenously every 2 weeks for 3 cycles or 42 days. | Drug | Avelumab |
Primary outcome
Change in T Cell Subpopulations
Time frame: pre-study time and 2-3 week post-operation
The change in T cell subpopulations (CD8, CD4 and/or CD3) in tumor samples will be collected from FFPE tissue. FFPE tissue from the pre-study time point refers to tissue from the TURBT. FFPE tissue from the 2-3 week post-op time point refers to FFPE tissue from the RC
3 secondary outcomes
Pathological Response Rate
Time frame: pre-study time and 2-3 week post-operation
2 Year Disease Free Survival (DFS)
Time frame: 2 years after radical cystectomy
Rate of High Grade(Grade 3-4) Adverse Event
Time frame: 90 days post operation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23141776Fairey 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.
- Background: PubMed 25872978Galsky 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.
- Background: PubMed 12944571Grossman 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.
- Background: PubMed 17980060Herchenhorn 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.
- Background: PubMed 21502557International 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.
- Background: PubMed 24821881Plimack 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.
- Background: PubMed 26184106van 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.
- Background: PubMed 14713760Winquist 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.
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- Background: PubMed 23123547Yuh 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.
- Background: PubMed 15939524Advanced 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.
- Background: PubMed 9366300Bellmunt 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.
- SITC 2016: Immune Checkpoint Inhibitors Shrink Tumors in Some Patients With Metastatic Bladder CancerLink provided by the sponsor.
- Cardiac Complications in Patients Receiving Combination Checkpoint Inhibitors Are Rare but Can Be FatalLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer M. Taylor, MD principal investigator
Baylor College of Medicine
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Avelumab in people with Bladder Cancer and Metastatic Bladder Cancer, run by Baylor College of Medicine at 3 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 20 inclusion and 23 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 24 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 24 Aug 2020). 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?
Change in T Cell Subpopulations (time frame: pre-study time and 2-3 week post-operation). 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 NCT03498196, which also lists 29 linked publications.
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 24 Aug 2020.