Trial Title:
Chemotherapy and Sequential Immunotherapy for Locally Advanced Urothelial Cancer
NCT ID:
NCT05600127
Condition:
Urothelial Carcinoma
Conditions: Official terms:
Carcinoma, Transitional Cell
Avelumab
Conditions: Keywords:
Chemotherapy
Immunotherapy
Safety
Pathological response
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Masking description:
single arm study, therefore no masking possible
Intervention:
Intervention type:
Drug
Intervention name:
Avelumab
Description:
3 cycles of avelumab (800mg, every 2 weeks)
Arm group label:
Avelumab
Other name:
Bavencio
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Amphia ziekenhuis
Address:
City:
Breda
Zip:
4818 CK
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Westgeest
Investigator:
Last name:
Leijte
Email:
Principal Investigator
Investigator:
Last name:
Westgeest
Email:
Principal Investigator
Facility:
Name:
Jeroen Bosch ziekenhuis
Address:
City:
Den Bosch
Zip:
5223 GZ
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Smilde
Investigator:
Last name:
Smilde
Email:
Principal Investigator
Facility:
Name:
Radboud UMC
Address:
City:
Nijmegen
Zip:
6525 GD
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Mehra
Investigator:
Last name:
vd Heijden
Email:
Principal Investigator
Investigator:
Last name:
Mehra
Email:
Principal Investigator
Facility:
Name:
Erasmus MC
Address:
City:
Rotterdam
Zip:
3015 GD
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Boormans
Email:
chasit@erasmusmc.nl
Start date:
December 1, 2022
Completion date:
December 2026
Lead sponsor:
Agency:
Erasmus Medical Center
Agency class:
Other
Collaborator:
Agency:
Merck KGaA, Darmstadt, Germany
Agency class:
Industry
Source:
Erasmus Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05600127
