Invasive Bladder CancerPhase 1BladderGATENCT04134000
Atezolizumab and BCG in High Risk BCG naïve Non-muscle Invasive Bladder Cancer (NMIBC) Patients (BladderGATE)
A Phase 1 study testing Atezolizumab and BCG in people with Invasive Bladder Cancer, run by Fundacion Oncosur at 1 site in Spain.
Trial summary
Patients with high-risk non-muscle invasive bladder cancer (NMIBC) are usually managed by transurethral resection of their bladder tumor (TURBT) alone plus additional intravesical therapy to deliver high local concentrations of a therapeutic agent within the bladder, potentially destroying viable tumor cells that… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Invasive Bladder Cancer
- What is being tested?
- Atezolizumab and BCG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteSpain
- Study dates
- 3 Feb 2020to Sep 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 ≥ 18 years old.
- Signed Informed Consent Form
- Histologically confirmed diagnosis of high risk non-muscle-invasive (T1, high grade Ta - G3- and / or carcinoma in situ) transitional cell carcinoma of the bladder
- Never treated with BCG or stopped >3y ago
- World Health Organization Performance Status (WHO PS) 0-1
- No prior radiation to bladder
Show all 13Show fewer
- Life expectancy ≥ 5 years
- Adequate hematologic and end-organ function
- The time elapsed between the TURBT and the start of the study treatment will not be less than 4 weeks or more than 12 weeks
- Women who are not postmenopausal or surgically sterile must have a negative serum pregnancy test result within 14 days prior to the first dose of study treatment.
- For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 150 days after the last dose of study drug.
- Tumor tissue biopsy at study entry or availability of an archival specimen obtained within 2 months of study screening
- Willingness to complete all study-related procedures including patient-reported questionnaires
Who cannot join
- Muscle-invasive, locally advanced non-resectable, or metastatic urothelial carcinoma (i.e., T2, T3, T4, and/or stage IV)
- Previous BCG within a 3 years period
- Life expectancy <5 years
- WHO PS 2, 3 or 4
- Known additional malignancy that is progressing or requires active treatment
- Active autoimmune disease that has required systemic treatment in the past 2 years
Show all 26Show fewer
- Evidence of interstitial lung disease or active non-infectious pneumonitis
- Active infection requiring systemic therapy
- Pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial through 150 days after the last dose of study treatment.
- Prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-ligand 2 (L2) agent, or with an agent directed to another co-inhibitory T-cell receptor
- Known human immunodeficiency virus (HIV)
- Known active Hepatitis B or C infection or tuberculosis
- Received a live virus vaccine within 30 days of planned start of study treatment
- Treatment with any approved anti-cancer therapy, including chemotherapy , radiation therapy , or hormonal therapy within 3 weeks prior to the first dose of study treatment
- Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to the first dose of study treatment
- Allergy or hypersensitivity to components of the atezolizumab or BCG formulation
- Prior allogeneic stem cell or solid organ transplantation
- History of idiopathic pulmonary fibrosis, organizing pneumonia , drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
- Serum albumin < 2.5 g/dL
- Severe infections within 4 weeks prior to the first dose of study treatment
- Signs or symptoms of infection within 2 weeks prior to the first dose of study treatment
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to the first dose of study treatment
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina
- Major surgical procedure other than for diagnosis within 4 weeks prior to the first dose of study treatment, or anticipation of need for a major surgical procedure during the course of the study
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
- History of prior systemic BCG infection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase Ib Trial of Atezolizumab and BCG in High Risk BCG naïve Non-muscle Invasive Bladder Cancer (NMIBC) Patients: BladderGATE Study
Patients with high-risk non-muscle invasive bladder cancer (NMIBC) are usually managed by transurethral resection of their bladder tumor (TURBT) alone plus additional intravesical therapy to deliver high local concentrations of a therapeutic agent within the bladder, potentially destroying viable tumor cells that remain following TURBT. Although the exact mechanism of bacillus Calmette-Guerin (BCG) antitumor action is unknown, its intravesical instillation triggers a variety of local immune responses, which appear to correlate with antitumor activity. BCG induction plus maintenance is the current, guideline-recommended standard of care for high-risk NMIBC. Both recent evidence and guidelines suggest that full-dose BCG maintenance after the first BCG dose of induction course as used in the SWOG 8507 and European Organization for Research and Treatment of Cancer (EORTC) 30911 and 30962 trials, is the most appropriate maintenance schedule. High-risk NMIBC patients following adequate treatment have a recurrence rate at 1 and 2 years of 25 and 30% respectively after treatment with the current standard (BCG), which is clearly unsatisfactory. Programmed death ligand 1 (PD-L1) is a surface glycoprotein that functions as an inhibitor of T-cells and plays a crucial role in suppression of cellular immune response. It is implicated in tumor immune escape by inducing apoptosis of activated antigen-specific CD8 T-cells, impairing cytokine production and diminishing the toxicity of activated T-cells. PD-L1 expression by immunohistochemistry using the Ventana SP142 assay on tumor-infiltrating immune cell (IC) status defined by the percentage of PD-L1 positive ICs: IC0 (<1%); IC1 (≥1% but<5%); and IC2/3 (≥5%PD-L1) has been demonstrated to be higher (IC2/3) in resection and TURBT specimens versus biopsies from primary lesions or metastatic sites. In patients with metastatic bladder cancer, treatment with the PD-L1 inhibitor atezolizumab (1200 mg, every 3 weeks) resulted in objective response rates of 26% in the IC2/3 group, 18% in the IC1/2/3 group and 15% in all patients. The median overall survival was 11.4 months in the IC2/3 group, 8.8 months in the IC1/2/3, and 7.9 months in all patients. Grade 3-4 related treatment-related adverse events occurred in 16% and grade 3-4 immune-mediated adverse events occurred in 5% of treated patients. In murine models with invasive bladder cancer, anti-PD-1 plus CpG has shown to increase survival in mice, with anti-PD-1 plus CpG being superior to either agent alone. Taken together, these results confirmed the clinical activity of atezolizumab in metastatic bladder cancer, which could be beneficial in patients with NMIBC in combination with standard approaches such as BCG.
- Conditions
- Invasive Bladder Cancer
- Being tested
- Atezolizumab, BCG
- Keywords
- non-muscle, bladder cancer, näive
- 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.
AtezolizumabDrug
1200 mg IV q3w until recurrence of disease, disease progression (e.g., muscle-invasive or metastatic UBC), symptomatic deterioration (i.e., uncontrollable pain secondary to disease or unmanageable ascites, etc.) attributed to disease progression as determined by the investigator, Intolerable toxicity related to atezolizumab, including development of an immune-mediated adverse event determined by the investigator to be unacceptable given the individual patient's potential response to therapy and severity of the event, any medical condition that may jeopardize the patient's safety if he or she continues on study treatment, use of another non-protocol anti-cancer therapy or pregnancy.
BCGDrug
1 or 1/2 instillation per week until recurrence of disease, disease progression (e.g., muscle-invasive or metastatic UBC), symptomatic deterioration (i.e., uncontrollable pain secondary to disease or unmanageable ascites, etc.) attributed to disease progression as determined by the investigator, Intolerable toxicity related to atezolizumab, including development of an immune-mediated adverse event determined by the investigator to be unacceptable given the individual patient's potential response to therapy and severity of the event, any medical condition that may jeopardize the patient's safety if he or she continues on study treatment, use of another non-protocol anti-cancer therapy or pregnancy.
| Study group | Role | What they receive |
|---|---|---|
| Atezolizumab + BCG | Experimental | Ten patient will be enrolled in first cohort, starting on level 0 (DL 0) receiving BCG 1 instillation per week and Atezolizumab 1200 mg IV every three weeks (q3w).
The next level of dose in case is necessary is BCG 1/2 instillation per week and Atezolizumab 1200 mg IV every three weeks (q3w) Receives: Drug: Atezolizumab; Drug: BCG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity (DLT)
Incidence and nature of DLT of BCG plus atezolizumab combination in NMIBC, graded according to NCI CTCAE v5.
Measured: Up to 24 months
Recurrence free survival.
Time from the date of start of treatment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to progression according to RECIST 1.1 as assessed by the Investigator
Measured: Up to 24 months
Secondary outcomes (3)
Incidence of Treatment-Emergent Adverse Events
Incidence of Adverse Events (AEs) per patient
Measured: Up to 24 months
Patient reported outcome
The change from baseline in patient-reported symptoms, function, and Health-related quality of life (HRQoL), as measured by the EORTC Quality of Life Questionnaire (QLQ)-C30.
Measured: Up to 24 months
Patient reported outcome
The change from baseline in patient-reported symptoms, function, and HRQoL, as measured by the EORTC Quality of Life Questionnaire (QLQ)-NMIBC24
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2019
- Study start3 Feb 2020
- Primary completionJun 2024 (estimated)
- Study completionSep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Invasive 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- open-label, non-randomized, dose de-escalation clinical trial with atezolizumab administered by IV infusion in combination with intravesical BCG.
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundacion Oncosur
- Sponsor type
- Research network
- Collaborators
- Apices Soluciones S.L.
- Responsible party
- Sponsor
- Investigators
- Daniel Castellano, MD, Principal investigator, Hospital 12 de Octubre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04134000
- Sponsor's protocol ID
- BladderGATE
- Other IDs
- 2019-002061-36, 2019
- Acronym
- BladderGATE
- Status last verified
- May 2024
- First submitted
- 16 Oct 2019
- Last updated
- 21 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Trial of Atezolizumab and BCG in High Risk BCG naïve Non-muscle Invasive Bladder Cancer (NMIBC) Patients: BladderGATE Study
- ClinicalTrials.gov ID
- NCT04134000
- Acronym / sponsor ID
- BladderGATE / BladderGATE
- Conditions
- Invasive Bladder Cancer
- Keywords
- non-muscle, bladder cancer, näive
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Fundacion OncosurResearch network
- Collaborators
- Apices Soluciones S.L.
- Study start
- 3 Feb 2020 (actual)
- Primary completion
- Jun 2024 (estimated)
- Study completion
- Sep 2024 (estimated)
- First posted
- 21 Oct 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.
Patients with high-risk non-muscle invasive bladder cancer (NMIBC) are usually managed by transurethral resection of their bladder tumor (TURBT) alone plus additional intravesical therapy to deliver high local concentrations of a therapeutic agent within the bladder, potentially destroying viable tumor cells that remain following TURBT. Although the exact mechanism of bacillus Calmette-Guerin (BCG) antitumor action is unknown, its intravesical instillation triggers a variety of local immune responses, which appear to correlate with antitumor activity. BCG induction plus maintenance is the current, guideline-recommended standard of care for high-risk NMIBC. Both recent evidence and guidelines suggest that full-dose BCG maintenance after the first BCG dose of induction course as used in the SWOG 8507 and European Organization for Research and Treatment of Cancer (EORTC) 30911 and 30962 trials, is the most appropriate maintenance schedule. High-risk NMIBC patients following adequate treatment have a recurrence rate at 1 and 2 years of 25 and 30% respectively after treatment with the current standard (BCG), which is clearly unsatisfactory. Programmed death ligand 1 (PD-L1) is a surface glycoprotein that functions as an inhibitor of T-cells and plays a crucial role in suppression of cellular immune response. It is implicated in tumor immune escape by inducing apoptosis of activated antigen-specific CD8 T-cells, impairing cytokine production and diminishing the toxicity of activated T-cells. PD-L1 expression by immunohistochemistry using the Ventana SP142 assay on tumor-infiltrating immune cell (IC) status defined by the percentage of PD-L1 positive ICs: IC0 (<1%); IC1 (≥1% but<5%); and IC2/3 (≥5%PD-L1) has been demonstrated to be higher (IC2/3) in resection and TURBT specimens versus biopsies from primary lesions or metastatic sites. In patients with metastatic bladder cancer, treatment with the PD-L1 inhibitor atezolizumab (1200 mg, every 3 weeks) resulted in objective response rates of 26% in the IC2/3 group, 18% in the IC1/2/3 group and 15% in all patients. The median overall survival was 11.4 months in the IC2/3 group, 8.8 months in the IC1/2/3, and 7.9 months in all patients. Grade 3-4 related treatment-related adverse events occurred in 16% and grade 3-4 immune-mediated adverse events occurred in 5% of treated patients. In murine models with invasive bladder cancer, anti-PD-1 plus CpG has shown to increase survival in mice, with anti-PD-1 plus CpG being superior to either agent alone. Taken together, these results confirmed the clinical activity of atezolizumab in metastatic bladder cancer, which could be beneficial in patients with NMIBC in combination with standard approaches such as BCG.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- open-label, non-randomized, dose de-escalation clinical trial with atezolizumab administered by IV infusion in combination with intravesical BCG.
| Arm | Type | Receives |
|---|---|---|
| Atezolizumab + BCG | Experimental | Drug: Atezolizumab, Drug: BCGTen patient will be enrolled in first cohort, starting on level 0 (DL 0) receiving BCG 1 instillation per week and Atezolizumab 1200 mg IV every three weeks (q3w). The next level of dose in case is necessary is BCG 1/2 instillation per week and Atezolizumab 1200 mg IV every three weeks (q3w) |
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 ≥ 18 years old.
- Signed Informed Consent Form
- Histologically confirmed diagnosis of high risk non-muscle-invasive (T1, high grade Ta - G3- and / or carcinoma in situ) transitional cell carcinoma of the bladder
- Never treated with BCG or stopped >3y ago
- World Health Organization Performance Status (WHO PS) 0-1
Key exclusion criteria (26 listed)
- Muscle-invasive, locally advanced non-resectable, or metastatic urothelial carcinoma (i.e., T2, T3, T4, and/or stage IV)
- Previous BCG within a 3 years period
- Life expectancy <5 years
- WHO PS 2, 3 or 4
- Known additional malignancy that is progressing or requires active treatment
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 |
|---|---|---|
| Atezolizumab1200 mg IV q3w until recurrence of disease, disease progression (e.g., muscle-invasive or metastatic UBC), symptomatic deterioration (i.e., uncontrollable pain secondary to disease or unmanageable ascites, etc.) attributed to disease progression as determined by the investigator, Intolerable toxicity related to atezolizumab, including development of an immune-mediated adverse event determined by the investigator to be unacceptable given the individual patient's potential response to therapy and severity of the event, any medical condition that may jeopardize the patient's safety if he or she continues on study treatment, use of another non-protocol anti-cancer therapy or pregnancy. | Drug | Atezolizumab + BCG |
| BCG1 or 1/2 instillation per week until recurrence of disease, disease progression (e.g., muscle-invasive or metastatic UBC), symptomatic deterioration (i.e., uncontrollable pain secondary to disease or unmanageable ascites, etc.) attributed to disease progression as determined by the investigator, Intolerable toxicity related to atezolizumab, including development of an immune-mediated adverse event determined by the investigator to be unacceptable given the individual patient's potential response to therapy and severity of the event, any medical condition that may jeopardize the patient's safety if he or she continues on study treatment, use of another non-protocol anti-cancer therapy or pregnancy. | Drug | Atezolizumab + BCG |
Primary outcome
Dose limiting toxicity (DLT)
Time frame: Up to 24 months
Incidence and nature of DLT of BCG plus atezolizumab combination in NMIBC, graded according to NCI CTCAE v5.
Recurrence free survival.
Time frame: Up to 24 months
Time from the date of start of treatment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to progression according to RECIST 1.1 as assessed by the Investigator
3 secondary outcomes
Incidence of Treatment-Emergent Adverse Events
Time frame: Up to 24 months
Patient reported outcome
Time frame: Up to 24 months
Patient reported outcome
Time frame: Up to 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2024.
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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.
Daniel Castellano, MD principal investigator
Hospital 12 de Octubre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Atezolizumab and BCG in people with Invasive Bladder Cancer, run by Fundacion Oncosur at 1 site 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 26 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: status not confirmed, as of the sponsor's last update on 21 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Dose limiting toxicity (DLT) (time frame: Up to 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 May 2024.