Non-muscle-invasive Bladder CancerPhase 2PREVERTNCT03950362
Bladder PREserVation by RadioTherapy and Immunotherapy in BCG Unresponsive Non-muscle Invasive Bladder Cancer
A Phase 2 study testing Avelumab and Radiotherapy in people with Non-muscle-invasive Bladder Cancer, run by Institut Paoli-Calmettes.
Trial summary
About two-thirds of newly diagnosed cases of bladder cancer are non-muscle-invasive bladder cancer (NMIBC). It is advocated that patients with high-risk NMIBC receive an adjuvant course of intravesical Bacille Calmette-Guerin (BCG) as first-line treatment. However, a substantial proportion of patients will 'fail' BCG. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-muscle-invasive Bladder Cancer
- What is being tested?
- Avelumab and Radiotherapy
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- No sites listed yet
- Study dates
- 15 Jun 2020to 15 Jun 2024
- Phase
- Phase 2
- 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
- Age ≥18 years.
- ECOG performance status ≤2.
- Patients having provided written informed consent prior to any study-related procedures.
- Life expectancy ≥ 12 months.
- High risk NMIBC (high grade, T1, or CIS) histologically confirmed by a systematic 2nd look complete re-TURBT.
- BCG unresponsive NMIBC defined as persistent high-grade disease at 6 months despite adequate BCG treatment (BCG refractory) or recurrence of high-grade disease within 6 months of the last BCG exposure (BCG relapsing disease).
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- Patient unfit for radical cystectomy because of age, comorbidities, or patient's refusal.
- No sign of pelvic involvement or distant metastasis on CT scan.
- Haematological and biological parameters allowing pelvic radiotherapy and anti-PDL1 administration:
- White blood cell count ≥4000/mm3
- Platelet count ≥100000 cells/mm3
- Haemoglobin level ≥9 g/dL or corrected after transfusion
- Glomerular filtration rate ≥25 mL/min.
- Adequate hepatic function: AST (SGOT) and ALT (SGPT) ≤2.5 x ULN, or ≤3.5 x ULN in the case of concurrent disease with known etiology and for which a corrective treatment is possible.
- Patients of childbearing potential: use of a medically acceptable method of contraception during the study and for 120 days after the last study treatment.
- Patients affiliated to the social security scheme.
- Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
Who cannot join
- Stage ≥pT2 tumors.
- Low grade recurrence / Ta recurrence after BCG therapy.
- Recurrence > 1 year after last BCG instillation.
- Prior pelvic irradiation.
- Histology other than urothelial or squamous cell carcinomas (e.g., adenocarcinomas, micropapillary, sarcomas, or small cell histological types).
- History of neoplastic disease, during the 3 years before registration, except completely resected cutaneous basal-cell carcinomas, carcinoma in-situ or localized prostate cancer without biochemical recurrence following definitive treatment.
- Prior treatment with CD137 agonists or immune checkpoint inhibitors, including anticytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4), anti-programmed death-1 receptor (anti-PD-1), and anti-programmed death-ligand 1 (anti-PD-L1) therapeutic antibodies.
- Contraindications for pelvic radiotherapy (e.g., inflammatory bowel disease).
Trial locations and contacts
No sites are listed yet.
About this study
About two-thirds of newly diagnosed cases of bladder cancer are non-muscle-invasive bladder cancer (NMIBC). It is advocated that patients with high-risk NMIBC receive an adjuvant course of intravesical Bacille Calmette-Guerin (BCG) as first-line treatment. However, a substantial proportion of patients will 'fail' BCG. Radical cystectomy remains the treatment of choice for NMIBC who have failed intravesical therapy, but there are situations when surgery is not feasible due to competing co-morbidities or a patient's desire for bladder preservation. For these patients, the potential options available are limited.
In MIBC, radiotherapy (RT) in association with chemotherapy, has been shown to produce 10-year overall survival rates comparable to those of radical cystectomy in selected cases. At the opposite, results from trials assessing radiotherapy with or without chemotherapy in patients with NMIBC are less documented and discordant.
Read more
Immunotherapy with immune-checkpoint blockade therapies is increasing as an option and has shown very promising results for several cancers, including bladder carcinoma.
An established body of published work has shown that radiation enhances many of the steps needed for the generation of antigen-specific immune responses, including inflammatory tumor-cell death, dendritic cell activation, and antigen cross-presentation. Several groups have reported improved local control when checkpoint blockade immunotherapy is added to radiation in different tumor types. On the one hand, radiotherapy might stimulate the induction of local endogenous immune responses by anti-PD-1 treatment. On the other hand, active immune stimulation by anti-PD-1 treatment within the tumor microenvironment might maximize radiation-induced antitumor immunity.
Combination immunoradiotherapy using PD-1/PD-L1 signaling blockade could therefore offer an interesting strategy in bladder tumors, especially as an optional bladder preservation treatment for BCG unresponsive NMIBC.
The originality of the therapeutic strategy is the use of radiation (local treatment) combined with checkpoint blockade immunotherapy (systemic treatment). Radiotherapy might increase response rates by creating a more permissive tumor microenvironment through increasing PD-L1 expression on tumor cells and stimulating the accumulation and activation of CD8+ T cells.
Avelumab seems to have a specific cytotoxic activity suggesting its interest in local control of the disease, especially in association with radiotherapy.
- Conditions
- Non-muscle-invasive Bladder Cancer
- Being tested
- Avelumab, Radiotherapy
- Keywords
- non-muscle-invasive bladder cancer, radiotherapy, immunotherapy, quality of life
- Medical subject headings
- 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
Administration of Avelumab 10mg/kg Infuse IV over 30-minutes: 1 cycle 5 days before External Beam RadioTherapy, then every 21 days x 8 cycles (6 months)
RadiotherapyDevice
60-66 Gy in 30-33 Fractions (2 Gy/fractions) given to the whole bladder
| Study group | Role | What they receive |
|---|---|---|
| Radiotherapy associated to immunotherapy | Experimental | * Radiotherapy: 60-66 Gy in 30-33 Fractions (2 Gy/fractions) given to the whole bladder
* Concomitant administration of Avelumab 10mg/kg Infuse IV over 30-minutes: 1 cycle 5 days before External Beam RadioTherapy, then every 21 days x 8 cycles (6 months) Receives: Drug: Avelumab; Device: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
High-risk recurrence-free survival at 1 year
Delay between date of inclusion and reappearance of high-risk disease (high grade, T1, or CIS) at cystoscopy
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2019
- Study start15 Jun 2020 (estimated)
- Primary completion15 Jun 2023 (estimated)
- Study completion15 Jun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-muscle-invasive Bladder CancerStudies of the same condition, open and under way.
- More trials run by Institut Paoli-CalmettesThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 67 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut Paoli-Calmettes
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03950362
- Sponsor's protocol ID
- prevert-IPC 2018-046
- Acronym
- PREVERT
- Status last verified
- May 2019
- First submitted
- 13 May 2019
- Last updated
- 16 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bladder PREserVation by RadioTherapy and Immunotherapy in BCG Unresponsive Non-muscle Invasive Bladder Cancer
- ClinicalTrials.gov ID
- NCT03950362
- Acronym / sponsor ID
- PREVERT / prevert-IPC 2018-046
- Conditions
- Non-muscle-invasive Bladder Cancer
- Keywords
- non-muscle-invasive bladder cancer, radiotherapy, immunotherapy, quality of life
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 67 participants (estimated)
- Lead sponsor
- Institut Paoli-CalmettesUniversity, hospital or other
- Study start
- 15 Jun 2020 (estimated)
- Primary completion
- 15 Jun 2023 (estimated)
- Study completion
- 15 Jun 2024 (estimated)
- First posted
- 15 May 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.
About two-thirds of newly diagnosed cases of bladder cancer are non-muscle-invasive bladder cancer (NMIBC). It is advocated that patients with high-risk NMIBC receive an adjuvant course of intravesical Bacille Calmette-Guerin (BCG) as first-line treatment. However, a substantial proportion of patients will 'fail' BCG. Radical cystectomy remains the treatment of choice for NMIBC who have failed intravesical therapy, but there are situations when surgery is not feasible due to competing co-morbidities or a patient's desire for bladder preservation. For these patients, the potential options available are limited.
In MIBC, radiotherapy (RT) in association with chemotherapy, has been shown to produce 10-year overall survival rates comparable to those of radical cystectomy in selected cases. At the opposite, results from trials assessing radiotherapy with or without chemotherapy in patients with NMIBC are less documented and discordant.
Immunotherapy with immune-checkpoint blockade therapies is increasing as an option and has shown very promising results for several cancers, including bladder carcinoma.
An established body of published work has shown that radiation enhances many of the steps needed for the generation of antigen-specific immune responses, including inflammatory tumor-cell death, dendritic cell activation, and antigen cross-presentation. Several groups have reported improved local control when checkpoint blockade immunotherapy is added to radiation in different tumor types. On the one hand, radiotherapy might stimulate the induction of local endogenous immune responses by anti-PD-1 treatment. On the other hand, active immune stimulation by anti-PD-1 treatment within the tumor microenvironment might maximize radiation-induced antitumor immunity.
Combination immunoradiotherapy using PD-1/PD-L1 signaling blockade could therefore offer an interesting strategy in bladder tumors, especially as an optional bladder preservation treatment for BCG unresponsive NMIBC.
The originality of the therapeutic strategy is the use of radiation (local treatment) combined with checkpoint blockade immunotherapy (systemic treatment). Radiotherapy might increase response rates by creating a more permissive tumor microenvironment through increasing PD-L1 expression on tumor cells and stimulating the accumulation and activation of CD8+ T cells.
Avelumab seems to have a specific cytotoxic activity suggesting its interest in local control of the disease, especially in association with radiotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Radiotherapy associated to immunotherapy | Experimental | Drug: Avelumab, Device: Radiotherapy* Radiotherapy: 60-66 Gy in 30-33 Fractions (2 Gy/fractions) given to the whole bladder * Concomitant administration of Avelumab 10mg/kg Infuse IV over 30-minutes: 1 cycle 5 days before External Beam RadioTherapy, then every 21 days x 8 cycles (6 months) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Age ≥18 years.
- ECOG performance status ≤2.
- Patients having provided written informed consent prior to any study-related procedures.
- Life expectancy ≥ 12 months.
- High risk NMIBC (high grade, T1, or CIS) histologically confirmed by a systematic 2nd look complete re-TURBT.
Key exclusion criteria (8 listed)
- Stage ≥pT2 tumors.
- Low grade recurrence / Ta recurrence after BCG therapy.
- Recurrence > 1 year after last BCG instillation.
- Prior pelvic irradiation.
- Histology other than urothelial or squamous cell carcinomas (e.g., adenocarcinomas, micropapillary, sarcomas, or small cell histological types).
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 |
|---|---|---|
| AvelumabAdministration of Avelumab 10mg/kg Infuse IV over 30-minutes: 1 cycle 5 days before External Beam RadioTherapy, then every 21 days x 8 cycles (6 months) | Drug | Radiotherapy associated to immunotherapy |
| Radiotherapy60-66 Gy in 30-33 Fractions (2 Gy/fractions) given to the whole bladder | Device | Radiotherapy associated to immunotherapy |
Primary outcome
High-risk recurrence-free survival at 1 year
Time frame: 1 year
Delay between date of inclusion and reappearance of high-risk disease (high grade, T1, or CIS) at cystoscopy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2019.
- 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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Avelumab and Radiotherapy in people with Non-muscle-invasive Bladder Cancer, run by Institut Paoli-Calmettes.
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 17 inclusion and 8 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 16 May 2019. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dominique Genre, MD (+33491223778, drci.up@ipc.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
High-risk recurrence-free survival at 1 year (time frame: 1 year). 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 16 May 2019.