Treatment Of Metastatic Bladder cancer at the time Of biochemical reLApse following radical cystectomy - TOMBOLA

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Midtjylland

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12], Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

26 Sep 2019 → ongoing

Decision date (initial)

2024-06-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Roche

External identifiers

EU CT number

2024-510865-41-00

EudraCT number

2019-001679-36

ClinicalTrials.gov

NCT04138628

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Complete response (CR) after treatment with investigational agent initiated by ctDNA positive statusafter radical cystectomy (with or without concomitant visible metastases on CT). Data will becompared to available historical data on response to PD-1 / PD-L1 targeted agents14,15. CR in thecurrent study is defined as ctDNA negative status in the last plasma samples taken during IOtreatment combined with negative imaging (CT) at the same time point after treatment. Thus, anymetastasis visible on CT at the time of treatment initiation should undergo complete response. InStudy Subjects without visible metastasis on CT at the time of treatment, initiation should result inunchanged status on CT.

Secondary objectives 11

1. Duration of freedom from clinical relapse in Study Subjects showing decrease or stabilization ofctDNA level after treatment with investigational agent
2. Overall survival after cystectomy in Study Subjects having biochemical relapse
3. Cancer specific survival after cystectomy in Study Subjects having biochemical relapse
4. Recurrence free survival after cystectomy in Study Subjects having biochemical relapse
5. Cancer specific survival after cystectomy in Study Subjects having biochemical relapse stratified for potential predictive biomarkers for response to treatment
6. Response rate to investigated agent stratified for PD-L1 expression and other predictive biomarkers like TMB, immune cell infiltration, tumor subtypes etc.
7. Response rate to neoadjuvant chemotherapy measured as down staging to T0 or T<2 at cystectomy and correlation with level of ctDNA in plasma and urine samples
8. Time to recurrence seen on imaging (symptomatic or asymptomatic)
9. Quality of life assessment using the EORTC QLQ 30 (Quality of life in cancer patients) and QLQ-BLM30 (Quality of life in patients with Muscle Invasive Bladder Cancer)
10. Cost-effectiveness modelling analysis
11. Prolonged CR defined as ctDNA negative status in the plasma samples taken 12 months following completion of IO combined with negative imaging (CT) at the same time point, without administration of other oncologic treatment

Conditions and MedDRA coding

Urothelial cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. ≥18 years of age at the time of signing the Informed Consent Form
2. For male Study Subjects: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm
3. Signed Informed Consent Form
4. ECOG PS 0 or 1
5. Is, according to the Investigator’s judgement, able to comply with the trial protocol
6. Ability to understand the Participant Information Sheet orally and in writing
7. Preoperative PET/CT of thorax, abdomen, and pelvis with no suspicion of organ metastases or lymph node metastasis* above the aortic bifurcation
8. Study Subjects planned to undergo radical cystectomy due to histopathological or clinical documented muscle invasive urothelial carcinoma (including subtypes) stage cT2-4a in the urinary bladder following NAC** in cisplatin-fit Study Subjects

Exclusion criteria 9

1. Other histology of BC than urothelial carcinoma – mixed tumours with urothelial features are allowed
2. Concomitant invasive cancer within 5 years other than non-melanoma skin cancer and prostate cancer without metastasis
3. Known contraindication to immunotherapy
4. A history of autoimmune disease. Study Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
5. Study Subjects who meet any of the following criteria will be excluded from study entry: o History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan o Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment
6. HIV positive
7. History of pneumonitis (History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
8. Hepatitis B or hepatitis C infection
9. Subjects who have received a live, attenuated vaccine within 28 days prior to enrolment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Complete response (CR) after treatment with investigational agent initiated by ctDNA positive status after radical cystectomy (with or without concomitant visible metastases on CT)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Midtjylland

Sponsor organisation

Region Midtjylland

Address

Palle Juul-Jensens Boulevard 99

City

Aarhus N

Postcode

8200

Country

Denmark

Scientific contact point

Organisation

Aarhus Universitetshospital

Contact name

Jørgen Bjerggaard Jensen

Public contact point

Organisation

Aarhus Universitetshospital

Contact name

Mads Agerbææk

Third parties 1

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications