Patients with metastatic urothelial carcinoma in treatment with pembrolizumab, as clinically indicated, beyond the First RECIST-defined progression who have a stable performance status and demonstrated clinical benefit without rapid disease progression MedDRA version: 21.0 Level: LLT Classification code 10046722 Term: Urothelial carcinoma bladder stage IV System Organ Class: 100000004864
Conditions
Interventions
Trade Name: ENDOXAN BAXTER - 50 MG COMPRESSE RIVESTITE 50 COMPRESSE
Product Name: CICLOFOSFAMIDE
Product Code: [2907]
Pharmaceutical Form: Tablet
INN or Proposed INN: Ciclofosfamide monoidrata
CAS Num
Sponsors
ISTITUTI FISIOTERAPICI OSPITALIERI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age = 18 years; • Histological diagnosis of urothelial carcinoma, Advanced or metastatic disease; • PD-L1 expression: PD-L1 determined by immunohistochemistry (IHC; Dako 22C3 pharmDx assay; Agilent Technologies) at a local laboratory, with expressions scored using the combined positive score (CPS); • Eastern Cooperative Oncology Group performance status (ECOG PS) =2; • Adequate hematologic, renal, and hepatic function; RECIST 1.1 measurable disease; • Ongoing Pembrolizumab, as clinically indicated (progression after platinum-based chemotherapy); • Progression disease according to RECIST criteria; Criteria for receiving ICIs beyond RECIST v1.1 progression are: clinical benefit assessed by investigator, stable performance status, tolerance of treatment and no need to deliver immediate intervention to prevent serious complication of progression; iUPD(immune unconfirmed progressive disease according to iRECIST criteria); which require radiological confirmation; Oligometastatic disease: minimal metastatic state in which patients have a low burden of metastatic disease with only a small number of metastatic sites at initial presentation of their illness; Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 23
Exclusion criteria
Exclusion criteria: • Condition requiring treatment with glucocorticoids (equivalent to >10 mg of prednisone daily); • Hyperprogression condiction definited as two-fold or greater increase in the tumor growth rate in terms of volume during immunotherapy or a time to treatment failure of less than 2 months or a greater than 50% increase in tumor burden in two diameters according to irRC compared with pre-immunotherapy imaging that was obtained within 2 months of the initiation of the immuno-oncology agent, or a greater than two fold increase in progression pace with one diameter or a two fold or greater increase in the tumor growth rate in one diameter on immunotherapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary end point is: non progressive rate at 6 months;Secondary Objective: The secondary end points are: duration of response (DOR); disease control rate (DCR); time to progression (TTP); OS; safety. Exploratory Endpoints: To identify biomarkers in blood and tissue samples to evaluate the mechanism of immune-resistance Immunogenicity of pembrolizumab given in combination with metronomic cyclophoshamide;Primary end point(s): Non progressive rate at 6 months;Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Response Rate;Timepoint(s) of evaluation of this end point: 3 months | — |
Countries
Italy
Contacts
Public ContactUOC ONCOLOGIA MEDICA 1
REGINA ELENA NATIONAL CANCER INSTITUTE
Outcome results
None listed