Efficacy of Atezolizumab Concurrent With Radiotherapy in Patients With Muscle-invasive Bladder cáncer
NCT ID: NCT04186013
Last Updated: 2022-10-26
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
ACTIVE_NOT_RECRUITING
Clinical Phase
PHASE2
Total Enrollment
39 participants
Study Classification
INTERVENTIONAL
Study Start Date
2019-09-18
Study Completion Date
2027-05-31
Brief Summary
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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.
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PHASE2
Detailed Description
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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
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
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Bladder Cancer
Study Design
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Allocation Method
NA
Intervention Model
SINGLE_GROUP
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
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Experimental arm
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)
Group Type
EXPERIMENTAL
Atezolizumab Injection [Tecentriq]
Intervention Type
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)
Intervention Type
RADIATION
60 Gy of radiotherapy in 30 fractions overs 6 weeks at 2 Gy/day
Interventions
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Atezolizumab Injection [Tecentriq]
intravenous infusion of 1.200 mg of Atezolizumab administered intravenously every 3 weeks for a total of 6 doses
Intervention Type
DRUG
External Beam Radiation Therapy (EBRT)
60 Gy of radiotherapy in 30 fractions overs 6 weeks at 2 Gy/day
Intervention Type
RADIATION
Eligibility Criteria
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Inclusion Criteria
1. Patients must be 18 years of age or older.
2. 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.
3. Patients who refuse treatment with cisplatin-based chemotherapy or in whom treatment with cisplatin-based therapy is not appropriate.
4. Patients must have ECOG performance status 0 to 2.
5. Patients must have adequate bone marrow function as defined by absolute neutrophil count \>1.500/mm3; platelets \>100.000/mm3 and HB ≥ 9g/dl.
6. Patients must have adequate renal and liver function as defined by calculated creatinine clearance \>15ml/min.
7. Total bilirubin, SGOT (AST) and/or SGPT (ALT) \< 2,5 times the upper limit of normal.
8. 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).
9. 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).
10. 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.
11. 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.
12. 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).
13. A paraffin-embedded tumour sample must be available for the associate molecular study.
2. 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.
3. Patients who refuse treatment with cisplatin-based chemotherapy or in whom treatment with cisplatin-based therapy is not appropriate.
4. Patients must have ECOG performance status 0 to 2.
5. Patients must have adequate bone marrow function as defined by absolute neutrophil count \>1.500/mm3; platelets \>100.000/mm3 and HB ≥ 9g/dl.
6. Patients must have adequate renal and liver function as defined by calculated creatinine clearance \>15ml/min.
7. Total bilirubin, SGOT (AST) and/or SGPT (ALT) \< 2,5 times the upper limit of normal.
8. 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).
9. 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).
10. 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.
11. 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.
12. 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).
13. A paraffin-embedded tumour sample must be available for the associate molecular study.
Exclusion Criteria
1. 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.
2. Presence of regional lymph node or metastatic extension of the disease.
3. Concurrent treatment with other experimental drugs (within 30 days prior to study entry) or other anti-cancer therapy.
4. 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.
5. Evidence of tumour-related moderate/severe hydronephrosis unless stented or with nephrostomy to preserve renal function.
6. Extensive or multifocal bladder carcinoma in situ (CIS) precluding curative chemoradiotherapy.
7. 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.
8. Patients with serious uncontrolled infection.
9. Has a known history of active BT (Bacillus Tuberculosis).
10. Has known history of, or any evidence of active, non-infectious pneumonitis.
11. 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.
12. Positive test for hepatitis B virus surface antigen (HBVsAg) or hepatitis C virus ribonucleic acid antibody (HCV-Ab) indicating acute or chronic infection.
13. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
14. 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.
15. Women of child-bearing potential unwilling to be abstinent or use effective methods of birth control.
16. General medical or psychological conditions that would preclude appropriate informed consent or compliance with the protocol.
(1) 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.
2. Presence of regional lymph node or metastatic extension of the disease.
3. Concurrent treatment with other experimental drugs (within 30 days prior to study entry) or other anti-cancer therapy.
4. 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.
5. Evidence of tumour-related moderate/severe hydronephrosis unless stented or with nephrostomy to preserve renal function.
6. Extensive or multifocal bladder carcinoma in situ (CIS) precluding curative chemoradiotherapy.
7. 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.
8. Patients with serious uncontrolled infection.
9. Has a known history of active BT (Bacillus Tuberculosis).
10. Has known history of, or any evidence of active, non-infectious pneumonitis.
11. 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.
12. Positive test for hepatitis B virus surface antigen (HBVsAg) or hepatitis C virus ribonucleic acid antibody (HCV-Ab) indicating acute or chronic infection.
13. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
14. 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.
15. Women of child-bearing potential unwilling to be abstinent or use effective methods of birth control.
16. General medical or psychological conditions that would preclude appropriate informed consent or compliance with the protocol.
(1) 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.
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Roche Farma, S.A
INDUSTRY
Sponsor Role
collaborator
Dynamic Science S.L.
INDUSTRY
Sponsor Role
collaborator
Spanish Oncology Genito-Urinary Group
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Locations
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Althaia Xarxa Assintencial
Manresa, Barcelona, Spain
Site Status
Consorci Corporació Sanitària Parc Taulí
Sabadell, Barcelona, Spain
Site Status
Hospital Universitario Sant Joan de Reus
Reus, Tarragona, Spain
Site Status
Hospital Clínico Universitario San Cecilio
Granada, , Spain
Site Status
Hospital Universitario Lucus Augusti
Lugo, , Spain
Site Status
Hospital Universitario La Princesa
Madrid, , Spain
Site Status
Hospital HM Sanchinarro
Madrid, , Spain
Site Status
Complejo Hospitalario Universitario Ourense
Ourense, , Spain
Site Status
Hospital Universitario Central de Asturias
Oviedo, , Spain
Site Status
Hospital Arnau de Vilanova
Valencia, , Spain
Site Status
Countries
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Spain
References
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Related Links
Access external resources that provide additional context or updates about the study.
http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf
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. 2014
http://www.sogug.es/
Web page of the sponsor of the study
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
SOGUG-2017-A-IEC(VEJ)-4
Identifier Type: -
Identifier Source: org_study_id
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