Chemotherapy and Sequential Immunotherapy for Locally Advanced Urothelial Cancer

NCT05600127 | Recruiting Phase 2 DMC

• 1 other identifier: NL80678.078.22
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 4

Brief Summary

Patients with locally advanced or clinically node positive urothelial carcinoma treated with chemotherapy, will receive 3 cycles of avelumab, followed by radical surgery.

Conditions

Urothelial Carcinoma

Keywords

Chemotherapy; Immunotherapy; Safety; Pathological response

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate

  the proportion of patients without residual UC in the surgical resection specimen, ypT0N0 (carcinoma situ is allowed), in the intention-to-treat analysis.

  About 1 month after radical surgery

Secondary Outcomes (5)

• Survival

  24 months after radical surgery

• Adverse events

  90 days after administration of the last cycle of avelumab

• Surgical complications

  90 days after radical surgery

• Non-invasive urothelial cancer

  About 1 month after radical surgery

• Delay in surgery

  About 1 month after radical surgery

Study Arms (1)

Avelumab

EXPERIMENTAL

3 cycles of avelumab (Bavencio), 800mg intravenous instillation in 60 min, every 2 weeks.

Drug: Avelumab

Interventions

Avelumab DRUG

3 cycles of avelumab (800mg, every 2 weeks)

Also known as: Bavencio

Avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Have histologically confirmed urothelial carcinoma of the bladder, upper urinary tract or urethra; a maximum of 50% of aberrant histology is allowed.
• Have clinical stage cT4NxM0 or cTxN1-N3M0 as assessed by bimanual examination under anaesthesia, CT scan, MRI scan or PET-CT scan.
• Have at least stable disease after a minimum of 3 or a maximum of 4 cycles of induction chemotherapy with cisplatin / carboplatin + gemcitabine according to RECIST v1.1.
• Are fit and willing to undergo radical surgery with removal of lymph node template including all affected lymph nodes and the primary tumor.
• World Health Organisation performance status of 0-2.
• Provide written informed consent.
• Negative pregnancy test in women with childbearing potential.
• Adequate bone marrow function, including:
• Absolute neutrophil count (ANC) ≥1,500/mm3 or 1.5 x 109/L;
• Platelets ≥100 x 109/L;
• Hemoglobin ≥5.6 mmol/L (may have been transfused).
• Adequate renal function, defined as estimated creatinine clearance ≥30 mL/min as calculated by the CKD-EPI eGFR.
• Adequate liver function, including:
• Total serum bilirubin \<1.5 x upper limit of normal (ULN);

You may not qualify if:

• Predominant (\>50%) non-urothelial carcinoma histology in the diagnostic endoresection specimen of the bladder, urethra or upper urinary tract.
• Any test for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating acute or chronic infection.
• Have an estimated creatinin clearance as assessed by the CKD-EPI eGFR of \<30 ml/min.
• Persisting toxicity related to prior chemotherapy (Grade \>2 NCI CTCAE v5.0).
• ≤2 cycles of induction platinum-based chemotherapy received.
• Progression of disease during or following induction platinum-based chemotherapy, as assessed by RECIST v1.1.
• Distant metastatic disease.
• Previous pelvic radiation therapy.
• Breastfeeding women.
• Bilateral upper urinary tract urothelial carcinoma.
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
• Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism.
• Active infection requiring systemic therapy.
• Known severe hypersensitivity reactions to monoclonal antibodies (Grade 3), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of asthma symptom control per the Global Initiative for Asthma 2015).
• Known prior or suspected hypersensitivity to avelumab.

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (4)

Radboud UMC

Nijmegen, Gelderland, 6525 GD, Netherlands

RECRUITING

Jeroen Bosch ziekenhuis

's-Hertogenbosch, North Brabant, 5223 GZ, Netherlands

RECRUITING

Amphia ziekenhuis

Breda, North Brabant, 4818 CK, Netherlands

RECRUITING

Erasmus MC

Rotterdam, South Holland, 3015 GD, Netherlands

RECRUITING

Related Publications (1)

• Rutten VC, Salhi Y, Robbrecht GJ, de Wit R, van Leenders GJLH, Zuiverloon TCM, Boormans JL. The CHASIT study: sequential chemo-immunotherapy in patients with locally advanced urothelial cancer - a non-randomized phase II clinical trial. BMC Cancer. 2023 Jun 13;23(1):539. doi: 10.1186/s12885-023-10963-7.

  PMID: 37312054 DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

avelumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• J L Boormans, MD PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

J L Boormans, MD PhD

CONTACT

0031 10 7032612; j.boormans@erasmusmc.nl

V C Rutten, MD

CONTACT

v.rutten@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: single arm study, therefore no masking possible
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 26, 2022
• First Posted: October 31, 2022
• Study Start: December 1, 2022
• Primary Completion: April 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 8, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (4)