Bladder CancerPhase 2NCT04186013

Efficacy of Atezolizumab Concurrent With Radiotherapy in Patients With Muscle-invasive Bladder cáncer

A Phase 2 study testing Atezolizumab Injection [Tecentriq] and External Beam Radiation Therapy (EBRT) in people with Bladder Cancer, run by Spanish Oncology Genito-Urinary Group at 10 sites in Spain.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

Search all trials

Trial summary

Open, multicentre, phase II trial of atezolizumab with concurrent normofractionated radiotherapy in patients with localized muscle-invasive bladder cancer treated with a selective multimodality bladder conservative approach. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Bladder Cancer
What is being tested?: Atezolizumab Injection [Tecentriq] and External Beam Radiation Therapy (EBRT)
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 39 participants
Where: 10 sitesSpain
Study dates: 18 Sep 2019to May 2027
Phase: Phase 2
Are there results?: Not yet: the study is under way

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

Patients must be 18 years of age or older.
Patients have histologically-confirmed diagnosis of muscle-invasive urothelial carcinoma of the bladder, in clinical stages T2-4a N0 M0, who are not candidates for radical cystectomy by medical reasons, refusal or patient's choice.
Patients who refuse treatment with cisplatin-based chemotherapy or in whom treatment with cisplatin-based therapy is not appropriate.
Patients must have ECOG performance status 0 to 2.
Patients must have adequate bone marrow function as defined by absolute neutrophil count >1.500/mm3; platelets >100.000/mm3 and HB ≥ 9g/dl.
Patients must have adequate renal and liver function as defined by calculated creatinine clearance >15ml/min.

Show all 13Show fewer

Total bilirubin, SGOT (AST) and/or SGPT (ALT) < 2,5 times the upper limit of normal.
International Normalized Ration (INR) or Prothrombin Time (PT): ≤1.5 X ULN unless participant is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants).
Activated Partial Thromboplastin Time (aPTT): ≤1.5 X ULN unless participant is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants).
Female participant of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to registering the patient. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Female participants of childbearing potential should be willing to use two methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 5 months after the last dose of study medication. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy (1).
A paraffin-embedded tumour sample must be available for the associate molecular study.

Who cannot join

Previous treatment with radiotherapy to the bladder, systemic chemotherapy or immune checkpoint inhibitors. Prior intravesical BCG treatment for non-muscle invasive bladder cancer is allowed.
Presence of regional lymph node or metastatic extension of the disease.
Concurrent treatment with other experimental drugs (within 30 days prior to study entry) or other anti-cancer therapy.
History of prior malignancies within the preceding 5 years other than previously treated basal cell carcinoma of the skin, non-muscle invasive bladder cancer, incidental prostate carcinoma Stage T1a well differentiated prostatic carcinoma in men (Gleason = 3+3, PSA <5) and carcinoma in situ of the cervix.
Evidence of tumour-related moderate/severe hydronephrosis unless stented or with nephrostomy to preserve renal function.
Extensive or multifocal bladder carcinoma in situ (CIS) precluding curative chemoradiotherapy.

Show all 22Show fewer

Bulky T3/T4a tumours unsuitable for curative treatment (i.e. > 5 cm in any dimension). Tumours measures must be done post-TUR via CT scan.
Patients with serious uncontrolled infection.
Has a known history of active BT (Bacillus Tuberculosis).
Has known history of, or any evidence of active, non-infectious pneumonitis.
Autoimmune diseases other than vitiligo, type I diabetes mellitus, residual hypothyroidism requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
Positive test for hepatitis B virus surface antigen (HBVsAg) or hepatitis C virus ribonucleic acid antibody (HCV-Ab) indicating acute or chronic infection.
Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
Subjects with a condition requiring systemic treatment with either corticosteroids (equivalent to > 10 mg/day prednisone) or other immune-suppressive medications within 14 days of study drug administration.
Women of child-bearing potential unwilling to be abstinent or use effective methods of birth control.
General medical or psychological conditions that would preclude appropriate informed consent or compliance with the protocol.
Acceptable methods of effective contraception:
Complete sexual abstinence for 14 days before the start of study treatment to 5 months after completion of the investigational treatment.
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), or tubal ligation at least six weeks before taking study treatment.
Male sterilization (at least 6 months prior to screening). For female subjects on the study the vasectomized male partner should be the sole partner for that subject.
Intrauterine device or system with a documented failure less than 1%.
Double barrier method with spermicide.

Trial locations and contacts

10 sites in 1 country.

City, postcode or hospital

10 sites in 1 country

Spain10 sites

Hospital Clínico Universitario San Cecilio
Granada, 18016
Hospital Universitario Lucus Augusti
Lugo, 27003
Hospital Universitario La Princesa
Madrid, 28006
Hospital HM Sanchinarro
Madrid, 28050
Althaia Xarxa Assintencial
Manresa, Barcelona, 08243
Complejo Hospitalario Universitario Ourense
Ourense, 32005
Hospital Universitario Central de Asturias
Oviedo, 33011
Hospital Universitario Sant Joan de Reus
Reus, Tarragona, 43204
Consorci Corporació Sanitària Parc Taulí
Sabadell, Barcelona, 08208
Hospital Arnau de Vilanova
Valencia, 6015

Other trials in Spain

About this study

Official title: Efficacy of Atezolizumab Concurrent With Radiotherapy in Patients With Muscle-invasive Bladder cáncer (Study ATEZOBLADDERPRESERVE)

Read the detailed description

STUDY DESIGN:

Open, multicentre, phase II trial of atezolizumab with concurrent normofractionated radiotherapy in patients with histologically confirmed diagnosis of muscle-invasive urothelial carcinoma of the bladder.

The bladder preserving therapy include combined modality therapy with:

STUDY TREATMENTS:

Investigational product (atezolizumab/Tecentriq ®):

Route of administration: intravenous infusion.
Duration of treatment: 16 weeks.
Dosage: 1.200 mg intravenous every 3 weeks for a total of 6 doses. Atezolizumab is supplied as atezolizumab 1200 mg/20 mL vials (60 mg/mL) solution for intravenous infusion. After dilution, one mL of solution should contain approximately 4.4 mg of atezolizumab (1,200 mg/270 mL).

External Beam Radiation Therapy (EBRT): radiation

Duration of treatment: 6 weeks
Dosage: 60 Gy of radiotherapy in 30 fractions overs 6 weeks at 2Gy/day

STUDY POPULATION:

Adult patients (aged ≥18 years) with histologically confirmed diagnosis of muscle-invasive urothelial carcinoma of the bladder, in clinical stages T2-T4a who are not candidates for radical cystectomy by medical reasons, refusal or patient´s choice.

A total of 39 patients are estimated to be included in the study.

OBJECTIVES:

Primary objective:

The primary objective of the study is to determine the efficacy of atezolizumab concurrent with radiotherapy in terms of pathological complete response defined as a response of grade 5 according to Miller and Payne criteria in patients with muscle-invasive bladder cancer treated with bladder preservation intent.

Secondary objectives:

To evaluate overall survival (OS).
To evaluate disease specific survival (DSS).
To evaluate disease free survival (DFS).
To evaluate bladder intact disease-free survival (BIDFS).
To calculate the number of patients with muscle invasive and non-muscle invasive local failure (LF).
To determine the rate of distance metastases defined as the percentage of patients who develop metastases.
To determine to the rate of patients with bladder preserved.
To determine to the rate of immediate or late salvage cystectomy.
The safety profile and tolerability of the combination of atezolizumab with concurrent radiotherapy.

Exploratory objectives:

To determine the predictive role of the expression of PD-1 / PD-L1 and CD8 in terms of pCR, OS and DFS in bladder cancer patients treated with atezolizumab plus radiotherapy.
The correlation between the levels of IFN-γ, interleukin 6 (IL-6), interleukin 18 (IL-18), or ITAC (also called CXCL11 or IP-9) and the efficacy parameters (pCR, OS and DFS) of the treatment with atezolizumab plus radiotherapy.

STUDY VISITS AND PROCEDURES:

The study includes the following visits:

Screening: within the 28 days prior to starting the study treatment.
Baseline visit: the first day of cycle 1
Visits over the treatment period (16 weeks ± 7 days): from administration of the first dose of the study treatment to the administration of the last dose of atezolizumab or withdrawal from the treatment. Treatment will consist of the administration of atezolizumab at 1,200 mg intravenous every 3 weeks for 6 cycles
Post-treatment follow-up: includes the biopsy and safety visit 1-2 months after the last dose of atezolizumab and a subsequent 5 years follow-up period after.
End of study visit/ Early termination: In patients who end the study follow-up or prematurely withdraw from the study

Conditions: Bladder Cancer
Being tested: Atezolizumab Injection [Tecentriq], External Beam Radiation Therapy (EBRT)
Medical subject headings: Urinary Bladder Neoplasms

What participants receive

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

Atezolizumab Injection [Tecentriq]Drug
intravenous infusion of 1.200 mg of Atezolizumab administered intravenously every 3 weeks for a total of 6 doses
External Beam Radiation Therapy (EBRT)Radiation
60 Gy of radiotherapy in 30 fractions overs 6 weeks at 2 Gy/day

Study groups in NCT04186013
Study group	Role	What they receive
Experimental arm	Experimental	Atezolizumab 1200 mg intravenous infusion every 3 weeks for a total of 6 doses combined with External Beam Radiation Therapy (EBRT) (dosage: 60 Gy in 30 fractions overs 6 weeks at 2Gy/day) Receives: Drug: Atezolizumab Injection [Tecentriq]; Radiation: External Beam Radiation Therapy (EBRT)

What is being measured

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

Pathological complete response
Response of grade 5 according to Miller and Payne criteria
Measured: After the end of the treatment (16 weeks)

Secondary outcomes (9)

Overall survival
Time from the date of the beginning of protocol therapy to the date of death due to any cause
Measured: through study completion, up to 5 years
Disease specific survival
Time from start of treatment to the date of having evidence of distant metastases, nodal recurrence or recurrence within the radiotherapy field that could be salvaged in a curative fashion, what happens first
Measured: through study completion, up to 5 years
Disease free survival
Time from the date of start of protocol therapy to the date of recurrence of muscle invasive or non-invasive bladder carcinoma or metastases, what happens first
Measured: through study completion, up to 5 years
Bladder-intact disease-free survival
Time from the date of initiation of protocol therapy until the development of MIBC recurrence, regional pelvic recurrence, distant metastases, bladder cancer-related death or cystectomy, what happens first
Measured: through study completion, up to 5 years
Muscle invasive and non-muscle invasive local failure
defined as patients that do not achieve a pCR defined as a response of grade 5 according to Miller and Payne criteria and documented tumour recurrence after pCR
Measured: through study completion, up to 5 years
Rate of distant metastases
Percentage of patients who develop distant metastases. Defined as lymphonodal involvement above the bifurcation of the iliac vessels or in inquinal regions and metastases resulting from hematogenous spread
Measured: through study completion, up to 5 years
Rate of patients with bladder preserved
Rate of patients with bladder preserved at the time of the biopsy of the tumour performed between one and two months after the last dose of atezolizumab
Measured: through study completion, up to 5 years
Rate of immediate or late salvage cystectomy
Immediate will be evaluated at the time of the biopsy of the tumour performed between one and two months after the last dose of atezolizumab and late will be evaluated during the follow-up
Measured: through study completion, up to 5 years
The safety profile and tolerability of the combination of atezolizumab with concurrent radiotherapy
Collection of any adverse events and serious adverse events
Measured: through study completion, up to 5 years

Timeline

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

18 Sep 2019May 2027

First posted4 Dec 2019
Study start18 Sep 2019
Primary completionFeb 2027 (estimated)
Study completionMay 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (52)Papers the sponsor has linked to this study.
Other trials for Bladder CancerStudies of the same condition, open and under way.
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 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 39 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04186013
Sponsor's protocol ID: SOGUG-2017-A-IEC(VEJ)-4
Status last verified: Oct 2022
First submitted: 26 Nov 2019
Last updated: 26 Oct 2022
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015 Mar;65(2):87-108. doi: 10.3322/caac.21262. Epub 2015 Feb 4.
PubMed 25651787
Stenzl A, Burger M, Fradet Y, Mynderse LA, Soloway MS, Witjes JA, Kriegmair M, Karl A, Shen Y, Grossman HB. Hexaminolevulinate guided fluorescence cystoscopy reduces recurrence in patients with nonmuscle invasive bladder cancer. J Urol. 2010 Nov;184(5):1907-13. doi: 10.1016/j.juro.2010.06.148. Epub 2010 Sep 17.
PubMed 20850152
Geavlete B, Jecu M, Multescu R, Geavlete P. Narrow-band imaging cystoscopy in non-muscle-invasive bladder cancer: a prospective comparison to the standard approach. Ther Adv Urol. 2012 Oct;4(5):211-7. doi: 10.1177/1756287212454181.
PubMed 23024703
Naselli A, Introini C, Timossi L, Spina B, Fontana V, Pezzi R, Germinale F, Bertolotto F, Puppo P. A randomized prospective trial to assess the impact of transurethral resection in narrow band imaging modality on non-muscle-invasive bladder cancer recurrence. Eur Urol. 2012 May;61(5):908-13. doi: 10.1016/j.eururo.2012.01.018. Epub 2012 Jan 20.
PubMed 22280855
Xiong Y, Li J, Ma S, Ge J, Zhou L, Li D, Chen Q. A meta-analysis of narrow band imaging for the diagnosis and therapeutic outcome of non-muscle invasive bladder cancer. PLoS One. 2017 Feb 13;12(2):e0170819. doi: 10.1371/journal.pone.0170819. eCollection 2017.
PubMed 28192481
Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours. Eur Urol. 2016 Jul;70(1):106-119. doi: 10.1016/j.eururo.2016.02.028. Epub 2016 Mar 17.
PubMed 26996659
Murta-Nascimento C, Silverman DT, Kogevinas M, Garcia-Closas M, Rothman N, Tardon A, Garcia-Closas R, Serra C, Carrato A, Villanueva C, Dosemeci M, Real FX, Malats N. Risk of bladder cancer associated with family history of cancer: do low-penetrance polymorphisms account for the increase in risk? Cancer Epidemiol Biomarkers Prev. 2007 Aug;16(8):1595-600. doi: 10.1158/1055-9965.EPI-06-0743.
PubMed 17684133
Ploeg M, Aben KK, Kiemeney LA. The present and future burden of urinary bladder cancer in the world. World J Urol. 2009 Jun;27(3):289-93. doi: 10.1007/s00345-009-0383-3. Epub 2009 Feb 15.
PubMed 19219610
Madersbacher S, Hochreiter W, Burkhard F, Thalmann GN, Danuser H, Markwalder R, Studer UE. Radical cystectomy for bladder cancer today--a homogeneous series without neoadjuvant therapy. J Clin Oncol. 2003 Feb 15;21(4):690-6. doi: 10.1200/JCO.2003.05.101.
PubMed 12586807
Babjuk M, Bohle A, Burger M, Capoun O, Cohen D, Comperat EM, Hernandez V, Kaasinen E, Palou J, Roupret M, van Rhijn BWG, Shariat SF, Soukup V, Sylvester RJ, Zigeuner R. EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016. Eur Urol. 2017 Mar;71(3):447-461. doi: 10.1016/j.eururo.2016.05.041. Epub 2016 Jun 17.
PubMed 27324428
Arcangeli G, Arcangeli S, Strigari L. A systematic review and meta-analysis of clinical trials of bladder-sparing trimodality treatment for muscle-invasive bladder cancer (MIBC). Crit Rev Oncol Hematol. 2015 Apr;94(1):105-15. doi: 10.1016/j.critrevonc.2014.11.007. Epub 2014 Dec 4.
PubMed 25541350
Efstathiou JA, Spiegel DY, Shipley WU, Heney NM, Kaufman DS, Niemierko A, Coen JJ, Skowronski RY, Paly JJ, McGovern FJ, Zietman AL. Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience. Eur Urol. 2012 Apr;61(4):705-11. doi: 10.1016/j.eururo.2011.11.010. Epub 2011 Nov 12.
PubMed 22101114
James ND, Hussain SA, Hall E, Jenkins P, Tremlett J, Rawlings C, Crundwell M, Sizer B, Sreenivasan T, Hendron C, Lewis R, Waters R, Huddart RA; BC2001 Investigators. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012 Apr 19;366(16):1477-88. doi: 10.1056/NEJMoa1106106.
PubMed 22512481
Mak KS, Smith AB, Eidelman A, Clayman R, Niemierko A, Cheng JS, Matthews J, Drumm MR, Nielsen ME, Feldman AS, Lee RJ, Zietman AL, Chen RC, Shipley WU, Milowsky MI, Efstathiou JA. Quality of Life in Long-term Survivors of Muscle-Invasive Bladder Cancer. Int J Radiat Oncol Biol Phys. 2016 Dec 1;96(5):1028-1036. doi: 10.1016/j.ijrobp.2016.08.023. Epub 2016 Aug 24.
PubMed 27727064
Huddart RA, Birtle A, Maynard L, Beresford M, Blazeby J, Donovan J, Kelly JD, Kirkbank T, McLaren DB, Mead G, Moynihan C, Persad R, Scrase C, Lewis R, Hall E. Clinical and patient-reported outcomes of SPARE - a randomised feasibility study of selective bladder preservation versus radical cystectomy. BJU Int. 2017 Nov;120(5):639-650. doi: 10.1111/bju.13900. Epub 2017 May 29.
PubMed 28453896

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 26 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Efficacy of Atezolizumab Concurrent With Radiotherapy in Patients With Muscle-invasive Bladder cáncer (Study ATEZOBLADDERPRESERVE)
ClinicalTrials.gov ID: NCT04186013
Acronym / sponsor ID: SOGUG-2017-A-IEC(VEJ)-4
Conditions: Bladder Cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 39 participants (estimated)
Lead sponsor: Spanish Oncology Genito-Urinary GroupUniversity, hospital or other
Collaborators: Roche Farma, S.A, Dynamic Science S.L.
Study start: 18 Sep 2019 (actual)
Primary completion: Feb 2027 (estimated)
Study completion: May 2027 (estimated)
First posted: 4 Dec 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

STUDY DESIGN:

The bladder preserving therapy include combined modality therapy with:

STUDY TREATMENTS:

Investigational product (atezolizumab/Tecentriq ®):

Route of administration: intravenous infusion.
Duration of treatment: 16 weeks.
Dosage: 1.200 mg intravenous every 3 weeks for a total of 6 doses. Atezolizumab is supplied as atezolizumab 1200 mg/20 mL vials (60 mg/mL) solution for intravenous infusion. After dilution, one mL of solution should contain approximately 4.4 mg of atezolizumab (1,200 mg/270 mL).

External Beam Radiation Therapy (EBRT): radiation

Duration of treatment: 6 weeks
Dosage: 60 Gy of radiotherapy in 30 fractions overs 6 weeks at 2Gy/day

STUDY POPULATION:

A total of 39 patients are estimated to be included in the study.

OBJECTIVES:

Primary objective:

Secondary objectives:

To evaluate overall survival (OS).
To evaluate disease specific survival (DSS).
To evaluate disease free survival (DFS).
To evaluate bladder intact disease-free survival (BIDFS).
To calculate the number of patients with muscle invasive and non-muscle invasive local failure (LF).
To determine the rate of distance metastases defined as the percentage of patients who develop metastases.
To determine to the rate of patients with bladder preserved.
To determine to the rate of immediate or late salvage cystectomy.
The safety profile and tolerability of the combination of atezolizumab with concurrent radiotherapy.

Exploratory objectives:

To determine the predictive role of the expression of PD-1 / PD-L1 and CD8 in terms of pCR, OS and DFS in bladder cancer patients treated with atezolizumab plus radiotherapy.
The correlation between the levels of IFN-γ, interleukin 6 (IL-6), interleukin 18 (IL-18), or ITAC (also called CXCL11 or IP-9) and the efficacy parameters (pCR, OS and DFS) of the treatment with atezolizumab plus radiotherapy.

STUDY VISITS AND PROCEDURES:

The study includes the following visits:

Screening: within the 28 days prior to starting the study treatment.
Baseline visit: the first day of cycle 1
Visits over the treatment period (16 weeks ± 7 days): from administration of the first dose of the study treatment to the administration of the last dose of atezolizumab or withdrawal from the treatment. Treatment will consist of the administration of atezolizumab at 1,200 mg intravenous every 3 weeks for 6 cycles
Post-treatment follow-up: includes the biopsy and safety visit 1-2 months after the last dose of atezolizumab and a subsequent 5 years follow-up period after.
End of study visit/ Early termination: In patients who end the study follow-up or prematurely withdraw from the study

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Experimental arm	Experimental	Drug: Atezolizumab Injection [Tecentriq], Radiation: External Beam Radiation Therapy (EBRT)Atezolizumab 1200 mg intravenous infusion every 3 weeks for a total of 6 doses combined with External Beam Radiation Therapy (EBRT) (dosage: 60 Gy in 30 fractions overs 6 weeks at 2Gy/day)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

Patients must be 18 years of age or older.
Patients have histologically-confirmed diagnosis of muscle-invasive urothelial carcinoma of the bladder, in clinical stages T2-4a N0 M0, who are not candidates for radical cystectomy by medical reasons, refusal or patient's choice.
Patients who refuse treatment with cisplatin-based chemotherapy or in whom treatment with cisplatin-based therapy is not appropriate.
Patients must have ECOG performance status 0 to 2.
Patients must have adequate bone marrow function as defined by absolute neutrophil count >1.500/mm3; platelets >100.000/mm3 and HB ≥ 9g/dl.

Key exclusion criteria (22 listed)

Previous treatment with radiotherapy to the bladder, systemic chemotherapy or immune checkpoint inhibitors. Prior intravesical BCG treatment for non-muscle invasive bladder cancer is allowed.
Presence of regional lymph node or metastatic extension of the disease.
Concurrent treatment with other experimental drugs (within 30 days prior to study entry) or other anti-cancer therapy.
History of prior malignancies within the preceding 5 years other than previously treated basal cell carcinoma of the skin, non-muscle invasive bladder cancer, incidental prostate carcinoma Stage T1a well differentiated prostatic carcinoma in men (Gleason = 3+3, PSA <5) and carcinoma in situ of the cervix.
Evidence of tumour-related moderate/severe hydronephrosis unless stented or with nephrostomy to preserve renal function.

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
Atezolizumab Injection [Tecentriq]intravenous infusion of 1.200 mg of Atezolizumab administered intravenously every 3 weeks for a total of 6 doses	Drug	Experimental arm
External Beam Radiation Therapy (EBRT)60 Gy of radiotherapy in 30 fractions overs 6 weeks at 2 Gy/day	Radiation	Experimental arm

Primary outcome

Pathological complete response
Time frame: After the end of the treatment (16 weeks)
Response of grade 5 according to Miller and Payne criteria

9 secondary outcomes

Overall survival
Time frame: through study completion, up to 5 years
Disease specific survival
Time frame: through study completion, up to 5 years
Disease free survival
Time frame: through study completion, up to 5 years
Bladder-intact disease-free survival
Time frame: through study completion, up to 5 years
Muscle invasive and non-muscle invasive local failure
Time frame: through study completion, up to 5 years
Rate of distant metastases
Time frame: through study completion, up to 5 years
Rate of patients with bladder preserved
Time frame: through study completion, up to 5 years
Rate of immediate or late salvage cystectomy
Time frame: through study completion, up to 5 years
The safety profile and tolerability of the combination of atezolizumab with concurrent radiotherapy
Time frame: through study completion, up to 5 years

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2022.
Results publication: PubMed 25651787Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015 Mar;65(2):87-108. doi: 10.3322/caac.21262. Epub 2015 Feb 4.
Results publication: PubMed 20850152Stenzl A, Burger M, Fradet Y, Mynderse LA, Soloway MS, Witjes JA, Kriegmair M, Karl A, Shen Y, Grossman HB. Hexaminolevulinate guided fluorescence cystoscopy reduces recurrence in patients with nonmuscle invasive bladder cancer. J Urol. 2010 Nov;184(5):1907-13. doi: 10.1016/j.juro.2010.06.148. Epub 2010 Sep 17.
Results publication: PubMed 23024703Geavlete B, Jecu M, Multescu R, Geavlete P. Narrow-band imaging cystoscopy in non-muscle-invasive bladder cancer: a prospective comparison to the standard approach. Ther Adv Urol. 2012 Oct;4(5):211-7. doi: 10.1177/1756287212454181.
Results publication: PubMed 22280855Naselli A, Introini C, Timossi L, Spina B, Fontana V, Pezzi R, Germinale F, Bertolotto F, Puppo P. A randomized prospective trial to assess the impact of transurethral resection in narrow band imaging modality on non-muscle-invasive bladder cancer recurrence. Eur Urol. 2012 May;61(5):908-13. doi: 10.1016/j.eururo.2012.01.018. Epub 2012 Jan 20.
Results publication: PubMed 28192481Xiong Y, Li J, Ma S, Ge J, Zhou L, Li D, Chen Q. A meta-analysis of narrow band imaging for the diagnosis and therapeutic outcome of non-muscle invasive bladder cancer. PLoS One. 2017 Feb 13;12(2):e0170819. doi: 10.1371/journal.pone.0170819. eCollection 2017.
Results publication: PubMed 26996659Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours. Eur Urol. 2016 Jul;70(1):106-119. doi: 10.1016/j.eururo.2016.02.028. Epub 2016 Mar 17.
Results publication: PubMed 17684133Murta-Nascimento C, Silverman DT, Kogevinas M, Garcia-Closas M, Rothman N, Tardon A, Garcia-Closas R, Serra C, Carrato A, Villanueva C, Dosemeci M, Real FX, Malats N. Risk of bladder cancer associated with family history of cancer: do low-penetrance polymorphisms account for the increase in risk? Cancer Epidemiol Biomarkers Prev. 2007 Aug;16(8):1595-600. doi: 10.1158/1055-9965.EPI-06-0743.
Results publication: PubMed 19219610Ploeg M, Aben KK, Kiemeney LA. The present and future burden of urinary bladder cancer in the world. World J Urol. 2009 Jun;27(3):289-93. doi: 10.1007/s00345-009-0383-3. Epub 2009 Feb 15.
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Clinical Trial Facilitation Group. Recommendations related to contraception and pregnancy testing in clinical trials. Clinical Trial Facilitation Group. Recommendations related to contraception and pregnancy testing in clinical trials. 2014Link provided by the sponsor.
Web page of the sponsor of the studyLink provided by the sponsor.
Individual participant dataSharing planned: No

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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.

The record lists no contact. Use the official record to reach the sponsor.

10 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab Injection [Tecentriq] and External Beam Radiation Therapy (EBRT) in people with Bladder Cancer, run by Spanish Oncology Genito-Urinary Group at 10 sites in Spain.

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 13 inclusion and 22 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: under way, not looking for participants, as of the sponsor's last update on 26 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

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

What does this phase mean?

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

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Pathological complete response (time frame: After the end of the treatment (16 weeks)). 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 NCT04186013, which also lists 52 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 26 Oct 2022.