Chemotherapy and Sequential Immunotherapy for Locally Advanced Urothelial Cancer

NCT ID: NCT05600127

Last Updated: 2023-09-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-01
• Study Completion Date: 2026-12-31

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.

Detailed Description

Patients with locally advanced or clinically node positive urothelial carcinoma of the bladder, ureter or urethra (cT4NxM0 or cTxN1-N3M0) with at least stable disease after treatment with 3-4 cycles of platinum-based chemotherapy, will be treated with 3 cycles of avelumab (anti-PD-L1). If there are no signs of disease progression after avelumab treatment, radical surgery of the primary tumor and a pelvic lymph node dissection will follow.

Conditions

Urothelial Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Avelumab

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

Group Type: EXPERIMENTAL

Avelumab

Intervention Type: DRUG

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

Interventions

Avelumab

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

Intervention Type: DRUG

Other Intervention Names

Bavencio

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years.

2. Have histologically confirmed urothelial carcinoma of the bladder, upper urinary tract or urethra; a maximum of 50% of aberrant histology is allowed.

3. Have clinical stage cT4NxM0 or cTxN1-N3M0 as assessed by bimanual examination under anaesthesia, CT scan, MRI scan or PET-CT scan.

4. 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.

5. Are fit and willing to undergo radical surgery with removal of lymph node template including all affected lymph nodes and the primary tumor.

6. World Health Organisation performance status of 0-2.

7. Provide written informed consent.

8. Negative pregnancy test in women with childbearing potential.

9. Adequate bone marrow function, including:

1. Absolute neutrophil count (ANC) ≥1,500/mm3 or 1.5 x 109/L;

2. Platelets ≥100 x 109/L;

3. Hemoglobin ≥5.6 mmol/L (may have been transfused).

10. Adequate renal function, defined as estimated creatinine clearance ≥30 mL/min as calculated by the CKD-EPI eGFR.

11. Adequate liver function, including:

1. Total serum bilirubin <1.5 x upper limit of normal (ULN);

2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 x ULN.

Exclusion Criteria

1. Predominant (>50%) non-urothelial carcinoma histology in the diagnostic endoresection specimen of the bladder, urethra or upper urinary tract.

2. Any test for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating acute or chronic infection.

3. Have an estimated creatinin clearance as assessed by the CKD-EPI eGFR of <30 ml/min.

4. Prior exposure to immune-mediated therapy with exclusion of Bacillus-Calmette Guérin intravesical instillations, including but not limited to other anti-CTLA-4, anti PD-1, anti PD-L1, or anti-PD-L2 antibodies.

5. Persisting toxicity related to prior chemotherapy (Grade >2 NCI CTCAE v5.0).

6. A diagnosis of any other malignancy within 2 years prior to inclusion, except for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the breast or of the cervix, low grade prostate cancer on surveillance without any plans for treatment intervention, or prostate cancer that has been adequately treated with prostatectomy or radiotherapy and currently with no evidence of disease.

7. ≤2 cycles of induction platinum-based chemotherapy received.

8. Progression of disease during or following induction platinum-based chemotherapy, as assessed by RECIST v1.1.

9. Distant metastatic disease.

10. Previous pelvic radiation therapy.

11. Breastfeeding women.

12. Bilateral upper urinary tract urothelial carcinoma.

13. 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.

14. 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.

15. Active infection requiring systemic therapy.

16. 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).

17. Known prior or suspected hypersensitivity to avelumab.

18. Current use of immunosuppressive medication, EXCEPT the following:

1. Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection);

2. Systemic corticosteroids at (equivalent) doses of maximum 10 mg prednisone;

3. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).

19. Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressive therapy, or known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.

20. Vaccination within 4 weeks of the first dose of study treatment and while on trial is prohibited except for administration of inactivate vaccines (for example, inactivated influenza vaccines) or mRNA vaccines (for example, COVID-19 vaccines).

21. Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, and pneumonitis; psychiatric condition including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

Erasmus Medical Center

OTHER

Sponsor Role: lead

Responsible Party

J.L. Boormans, MD PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

J L Boormans, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Center

Locations

Radboud UMC

Nijmegen, Gelderland, Netherlands

Site Status: RECRUITING

Jeroen Bosch ziekenhuis

's-Hertogenbosch, North Brabant, Netherlands

Site Status: RECRUITING

Amphia ziekenhuis

Breda, North Brabant, Netherlands

Site Status: RECRUITING

Erasmus MC

Rotterdam, South Holland, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

J L Boormans, MD PhD

Role: CONTACT

j.boormans@erasmusmc.nl

0031 10 7032612

V C Rutten, MD

Role: CONTACT

v.rutten@erasmusmc.nl

Facility Contacts

Mehra

Role: primary

Smilde

Role: primary

Westgeest

Role: primary

Boormans

Role: primary

chasit@erasmusmc.nl

References

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.

Reference Type: DERIVED

PMID: 37312054 (View on PubMed)

Other Identifiers

NL80678.078.22

Identifier Type: -

Identifier Source: org_study_id