Treatment Of Metastatic Bladder Cancer at the Time Of Biochemical reLApse Following Radical Cystectomy (TOMBOLA)
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|ClinicalTrials.gov Identifier: NCT04138628|
Recruitment Status : Recruiting
First Posted : October 24, 2019
Last Update Posted : March 17, 2021
Immunotherapy (checkpoint inhibitors) is approved as first and second line treatment to patients with metastatic bladder cancer. However, response rates are low and no biomarkers have yet shown strong predictive value for patient selection. Moreover, the term 'metastatic' is based on metastases visible on conventional CT scans and, thus, require a certain size of tumour load. Clinical trials are currently being conducted that investigate the use of adjuvant immunotherapy for this group of patients (treatment to all), which will result in massive over-treatment and huge costs to the healthcare system.
This project has the primary objective to identify new indications for initiating immunotherapy in patients with metastatic bladder cancer. Sensitive molecular techniques for detection of tumor DNA in the blood will be used to identify patients with early signs of metastatic disease. In addition, comprehensive biomarker analysis will be performed to identify predictors of treatment response.
|Condition or disease||Intervention/treatment||Phase|
|Bladder Cancer Bladder Cancer, Metastatic||Drug: Atezolizumab||Phase 2|
The study aim at investigate the response rate and oncological outcome of systemic immunotherapy (PDL-1 inhibitor; atezolizumab) administered early at the time of biochemical relapse (circulating tumor DNA (ctDNA) positive) in patients who have undergone radical cystectomy because of muscle invasive bladder cancer.
Biomarkers that predict response to systemic immunotherapy will be identified by comprehensive multi-omics analysis of primary tumors and metastatic lesions. Furthermore, we will determine if ctDNA levels during therapy can be used as a biomarker for early indication of therapy response.
The hypotheses is that 1) early initiation of immunotherapy in high-risk (ctDNA positive) patients will result in better response rates and improved survival compared to later treatment following conventional imaging diagnosis of metastasis, and 2) biomarkers for predicting response can be identified and used for tailoring treatment regimens in the future to patients at high risk and at high likelihood of response.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||282 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Single country Investigator Initiated, Open-label, Single-arm, Non-randomized, Phase II study|
|Masking:||None (Open Label)|
|Official Title:||Treatment Of Metastatic Bladder Cancer at the Time Of Biochemical reLApse Following Radical Cystectomy|
|Actual Study Start Date :||March 24, 2020|
|Estimated Primary Completion Date :||August 1, 2022|
|Estimated Study Completion Date :||November 1, 2024|
Experimental: ctDNA screening arm
Flat dose 1200 mg Atezolizumab every three weeks for up to 13 months
The study drug will be given according to current recommendations as systemic treatment every third week for 12 months or until progression. Treatment will be initiated within 28 days of detection of ctDNA.
- Complete response (CR) after treatment with investigational agent initiated by ctDNA positive status after radical cystectomy (with or without concomitant visible metastases on CT). [ Time Frame: Time from treatment initiation with investigational agent until 12 months after initiation ]
CR in the current study is defined as ctDNA negative status combined with regular imaging (CT) after treatment. Thus, any metastasis visible on CT at the time of treatment initiation should undergo complete response. In Study Subjects without visible metastasis on CT at the time of treatment, initiation should result in unchanged status on CT.
Data will be compared to available historical data on response to PD-1 / PD-L1 targeted agents.
- Duration of freedom from clinical relapse in Study Subjects showing decrease or stabilization of ctDNA level after treatment with investigational agent [ Time Frame: 12 months ]Time from initiation of therapy until response
- Overall survival after cystectomy in Study Subjects having biochemical relapse [ Time Frame: 5 years ]Percentage
- Cancer specific survival after cystectomy in Study Subjects having biochemical relapse [ Time Frame: 5 years ]Percentage
- Recurrence free survival after cystectomy in Study Subjects having biochemical relapse [ Time Frame: 5 years ]Percentage
- Cancer specific survival after cystectomy in Study Subjects having biochemical relapse stratified for potential predictive biomarkers for response to treatment [ Time Frame: 5 years ]Percentage
- Response rate to investigated agent stratified for PD-L1 expression and other predictive biomarkers like TMB, immune cell infiltration, tumor subtypes etc. [ Time Frame: 12 months ]Percentage
- Time to recurrence seen on imaging (symptomatic or asymptomatic) [ Time Frame: 5 years ]Percentage
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04138628
|Contact: Jørgen B Jensen, MD, DMSc||+45 email@example.com|
|Contact: Lars Dyrskjøt, Professor||+45 firstname.lastname@example.org|
|Aalborg, Denmark, 9100|
|Contact: Astrid Livbjerg, MD +45 97663008|
|Principal Investigator: Astrid Livbjerg, MD|
|Principal Investigator: Andreas Carus, MD|
|Aarhus University Hospital||Recruiting|
|Aarhus, Denmark, 8200|
|Contact: Jørgen B Jensen, MD +4530915682 email@example.com|
|Principal Investigator: Mads Agerbæk, MD|
|Principal Investigator: Jørgen B Jensen, MD|
|Copenhagen, Denmark, 2100|
|Contact: Ulla N Joensen, MD +45 35452111|
|Principal Investigator: Ulla N Joensen, MD|
|Principal Investigator: Helle Pappot, MD|
|Herlev, Denmark, 2730|
|Contact: Gitte W Lam, MD +45 38680140|
|Principal Investigator: Line H Dohn, MD|
|Principal Investigator: Gitte W Lam, MD|
|Odense, Denmark, 5000|
|Contact: Thor K Jensen, MD +45 65414400|
|Principal Investigator: Thor K Jensen, MD|
|Principal Investigator: Niels V Jensen, MD|
|Principal Investigator:||Jørgen B Jensen, Professor||Dept. Of Urology, Aarhus University Hospital, Denmark|
|Study Chair:||Lars Dyrskjøt, Professor||Dept. Of Molecular Medicine (MOMA) Aarhus University Hospital, Denmark|
|Principal Investigator:||Mads Agerbæk, MD||Dept. Of Oncology, Aarhus University Hospital, Denmark|
|Study Chair:||Karin Birkenkamp-Demtröder, Ass. professor||Dept. Of Molecular Medicine (MOMA) Aarhus University Hospital, Denmark|