Early immunotherapy for metastatic bladder cancer after surgery

Treatment Of Metastatic Bladder Cancer at the Time Of Biochemical reLApse Following Radical Cystectomy

This study is testing if starting immunotherapy right after surgery can help people with advanced bladder cancer do better than the usual treatment.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 282 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Aarhus University Hospital (other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone, atezolizumab
• Locations: 5 sites (Aalborg and 4 other locations)
• Trial ID: NCT04138628 on ClinicalTrials.gov

What this trial studies

This study investigates the effectiveness of early immunotherapy using atezolizumab in patients with metastatic bladder cancer who have undergone radical cystectomy. It aims to identify patients with early signs of metastatic disease through sensitive molecular techniques that detect circulating tumor DNA (ctDNA) in the blood. The study will also analyze biomarkers from primary tumors and metastatic lesions to predict treatment response. The hypothesis is that initiating treatment early in high-risk patients will lead to better outcomes compared to traditional methods that rely on visible metastases.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older who have undergone radical cystectomy for muscle invasive bladder cancer and have detectable ctDNA.

Not a fit: Patients with no detectable ctDNA or those who have not undergone radical cystectomy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved survival rates and more personalized treatment for patients with metastatic bladder cancer.

How similar studies have performed: Other studies have explored immunotherapy in metastatic bladder cancer, but this approach focusing on early intervention based on ctDNA detection is relatively novel.

Eligibility criteria

Inclusion Criteria:

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

  * Study Subjects who have undergone down-staging chemotherapy because of lymph node metastasis with no organ metastases can be included if complete response regarding lymph nodes are identified on preoperative imaging.

    * NAC includes Study Subjects who have stopped after one course of chemotherapy because of side effects or local non-metastatic progression

Exclusion Criteria:

* Subjects undergoing non-radical cystectomy for palliative reasons
* Non-radical surgery estimated intraoperative
* Other histology of BC than urothelial carcinoma - mixed tumours with urothelial features are allowed
* Concomitant invasive cancer within 5 years other than non-melanoma skin cancer and prostate cancer without metastasis
* Known contraindication to immunotherapy
* 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.
* Study Subjects who meet any of the following criteria will be excluded from study entry:

  * 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
  * 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
* HIV positive
* History of pneumonitis (History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
* Hepatitis B or hepatitis C infection
* Subjects who have received a live, attenuated vaccine within 28 days prior to enrolment

Where this trial is running

Aalborg and 4 other locations

• Aalborg Universitetshospital — Aalborg, Denmark (RECRUITING)
• Aarhus University Hospital — Aarhus, Denmark (RECRUITING)
• Rigshospitalet — Copenhagen, Denmark (RECRUITING)
• Herlev Hospital — Herlev, Denmark (RECRUITING)
• Odense Universitetshospital — Odense, Denmark (RECRUITING)

Study contacts

• Principal investigator: Jørgen B Jensen, Professor — Dept. Of Urology, Aarhus University Hospital, Denmark
• Study coordinator: Jørgen B Jensen, MD, DMSc

Conditions: Bladder Cancer, Bladder Cancer, Metastatic, Muscle Invasive Bladder Cancer, biomarkers, ctDNA, immunotherapy, circulating tumor DNA, liquid biopsies