DaBlaCa-14

About this trial

Last updated 3 years ago

Study ID

DaBlaCa-14

Status

Recruiting

Type

Interventional

Phase

Phase 2

Placebo

Accepting

18+ Years

All

Not accepting

Healthy Volunteers

Trial Timing

Started 5 years ago

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.

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