Clinical Trials List
Protocol NumberL00070 IN312 P1
NCT Number(ClinicalTrials.gov Identfier)N/A
2015-09-24 - 2018-12-31
Phase III
Terminated4
ICD-9188.9
Malignant neoplasm of bladder, part unspecified
Randomized phase III study comparing vinflunine-gemcitabine and gemcitabine-carboplatin combinations in patients ineligible to cisplatin with advanced or metastatic urothelial carcinoma.
-
Trial Applicant
Orient EuroPharma Co., Ltd.
-
Sponsor
Pierre Fabre
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/19
Investigators and Locations
Co-Principal Investigator
- Shang-Yin Wu Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
- Wu-Chou Su Division of Hematology & Oncology
- Sin-Syue Li Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Chueh-Chuan Yen Division of Hematology & Oncology
- 沈書慧 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Yu-Chieh Tsai Division of Hematology & Oncology
- Yeong-Shiau Pu Division of Hematology & Oncology
- - - Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
Urothelial Carcinoma
Objectives
Primary objective:
To compare the median Progression Free Survival without related Severe Acute Toxicity*
between arms (called SAT-PFS).
*[enlarged definition of the Severe Acute Toxicity (SAT) from the EORTC study 30986
adding vinflunine specific risks: neutropenia G4 > 7 days, neutropenic fever G3/4,
neutropenic systemic sepsis G3/G4 (neutropenia G3/4), G3/G4 thrombocytopenia with
bleeding, G3/4 renal toxicity, G3/4 mucositis, constipation G4 requiring surgery, and
death].
Secondary objectives:
- To evaluate the Disease Control Rate (DCR) and the Objective Response Rate (ORR),
- To estimate the Duration of Response of Disease Control and of Stable Disease,
- To estimate the Progression-Free Survival (PFS), Time To Treatment Failure (TTF),
- To estimate the Overall Survival (OS).
- To assess the Tolerance.
- To assess the Quality of Life.
Test Drug
JAVLOR
Active Ingredient
Vinflunine ditartrate
Dosage Form
Injection
Dosage
50mg
250mg
250mg
Endpoints
- Efficacy assessment
Tumour assessment will be performed according to the RECIST guideline (version 1.1).
Assessment of measurable and non-measurable disease will be carried out at baseline and
every 6 weeks until disease progression.
Survival data and post-study treatments will be reported every 3 months after progression.
Progression and tumour response will be evaluated for all randomized patients by the
investigators.
Duration of disease control and response will be evaluated for all patients with disease
control and responding patients, respectively.
Moreover, clinical parameters such as pain intensity will be assessed every 2 cycles.
- Safety assessment
Safety measures: physical examination and vital signs, performance status, complete blood
counts, serum biochemistry, adverse events reporting using the NCI Common Toxicity
Criteria (version 4.0) grading.
Tumour assessment will be performed according to the RECIST guideline (version 1.1).
Assessment of measurable and non-measurable disease will be carried out at baseline and
every 6 weeks until disease progression.
Survival data and post-study treatments will be reported every 3 months after progression.
Progression and tumour response will be evaluated for all randomized patients by the
investigators.
Duration of disease control and response will be evaluated for all patients with disease
control and responding patients, respectively.
Moreover, clinical parameters such as pain intensity will be assessed every 2 cycles.
- Safety assessment
Safety measures: physical examination and vital signs, performance status, complete blood
counts, serum biochemistry, adverse events reporting using the NCI Common Toxicity
Criteria (version 4.0) grading.
Inclution Criteria
Inclusion criteria:
- Histologically confirmed diagnosis of locally advanced or metastatic predominantly
transitional cell carcinoma of the urothelium (TCC) [urinary bladder, kidney, renal
pelvis, or ureter],
- Man or woman aged ≥ 18 years and < 80 years,
- Signed written informed consent before completing any study-related procedure,
- Ineligibility for cisplatin-based therapy because of renal impaired function (calculated
creatinine clearance by Cockroft-Gault formula < 60 mL/min),
- Presence of a “measurable” disease which has not been previously irradiated with at least
one uni-dimensional lesion according to RECIST guideline (version 1.1),
- ECOG performance status of 0 or 1 and estimated life expectancy more than 12 weeks
- Patient without prior systemic anticancer therapy for TCC unless cytotoxic agents have
been administered in the peri-operative setting (neoadjuvant or adjuvant chemotherapy)
and if documented relapse is ≥ 6 months after the last dose of chemotherapy,
- Adequate bone marrow and hepatic functions as evidenced by:
o Absolute Neutrophil Count ≥ 2.0 x 109
/L, Platelet count ≥ 100 x 109
/L,
Haemoglobin ≥ 10.0 g/dL
o Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN), Transaminases ≤ 2.5
x ULN [≤ 5 x ULN only in case of liver metastasis]
- Absence of psychological, familial, sociological or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule; these conditions
should be assessed with the patient before randomization in the trial,
- Women of childbearing potential must be using a medically accepted method of
contraception to avoid pregnancy during the 2 months preceding the start of study
treatment, throughout the study period and for up to 6 months after the last dose of study
treatment; women of childbearing potential must have a negative serum or urine
pregnancy test within 72 hours prior to the start of study treatment,
- Fertile men must be using an effective method of birth control during the study and up to
6 months after the last dose of study treatment if their partners are women of childbearing
potential,
- Patient access to social insurance if applicable in the local regulation.
- Histologically confirmed diagnosis of locally advanced or metastatic predominantly
transitional cell carcinoma of the urothelium (TCC) [urinary bladder, kidney, renal
pelvis, or ureter],
- Man or woman aged ≥ 18 years and < 80 years,
- Signed written informed consent before completing any study-related procedure,
- Ineligibility for cisplatin-based therapy because of renal impaired function (calculated
creatinine clearance by Cockroft-Gault formula < 60 mL/min),
- Presence of a “measurable” disease which has not been previously irradiated with at least
one uni-dimensional lesion according to RECIST guideline (version 1.1),
- ECOG performance status of 0 or 1 and estimated life expectancy more than 12 weeks
- Patient without prior systemic anticancer therapy for TCC unless cytotoxic agents have
been administered in the peri-operative setting (neoadjuvant or adjuvant chemotherapy)
and if documented relapse is ≥ 6 months after the last dose of chemotherapy,
- Adequate bone marrow and hepatic functions as evidenced by:
o Absolute Neutrophil Count ≥ 2.0 x 109
/L, Platelet count ≥ 100 x 109
/L,
Haemoglobin ≥ 10.0 g/dL
o Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN), Transaminases ≤ 2.5
x ULN [≤ 5 x ULN only in case of liver metastasis]
- Absence of psychological, familial, sociological or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule; these conditions
should be assessed with the patient before randomization in the trial,
- Women of childbearing potential must be using a medically accepted method of
contraception to avoid pregnancy during the 2 months preceding the start of study
treatment, throughout the study period and for up to 6 months after the last dose of study
treatment; women of childbearing potential must have a negative serum or urine
pregnancy test within 72 hours prior to the start of study treatment,
- Fertile men must be using an effective method of birth control during the study and up to
6 months after the last dose of study treatment if their partners are women of childbearing
potential,
- Patient access to social insurance if applicable in the local regulation.
Exclusion Criteria
Exclusion criteria:
- ECOG performance status ≥ 2,
- Calculated creatinine clearance < 30 mL/min (Cockcroft-Gault formula),
- Known brain metastasis or leptomeningeal involvement (computed tomography scans
not required to rule this out unless there is clinical suspicion of central nervous system
disease),
- Peripheral neuropathy Grade ≥ 2 by National Cancer Institute Common Toxicity Criteria
[NCI CTC],
- Prior radiation to ≥ 30% of the bone marrow or completed < 30 days ago or without full
recovery of toxicities,
- Other serious concomitant/uncontrolled medical condition including:
o Infection requiring systemic anti-infective therapy within 2 weeks before
randomization or suspected sepsis
o Any medical condition that might not be controlled such as unstable angina,
myocardial infarction within the previous 6 months, unstable congestive heart
failure (NYHA Stage III-IV) or uncontrolled diabetes,
- Electrocardiogram (ECG) with significant modifications suggesting a high risk of
occurrence of an acute clinical event (such as signs of angina pectoris, high risk
arrhythmia, QT/QTc prolongation),
- Prior systemic immunotherapy for advanced or metastatic urothelium carcinoma,
- Prior systemic neoadjuvant/adjuvant chemotherapy that was completed < 6 months
before documented progression,
- Patient who had received any investigational drug within 30 days before randomisation
- History of another malignancy except adequately treated basal carcinoma of the skin, insitu cervix carcinoma, localised prostate cancer with limited risk of recurrence (pT ≤ 2b,
Gleason score ≤ 7) that did not lead to any other treatment apart from prostatectomy, or
any other tumor with a disease free interval ≥ 5 years,
- Patients who require treatment with ketoconazole, itraconazole, ritonavir, amprenavir,
indinavir, rifampicine (any potent CYP3A4 inhibitor or inducer), phenytoine or
medicinal products known to prolong QT/QTc interval,
- Known hypersensitivity to the study drugs or to drugs with similar chemical structures,
- Any previous organ allograft or any chronic system disease requiring concurrent immune
therapy,
- Woman if pregnant or lactating or with positive pregnancy test at inclusion; woman of
child-bearing potential who did not use or is unwilling or unable to use an acceptable
method to avoid pregnancy during the 2 months preceding the start of study treatment,
for the entire study period and for up to 6 months after the last dose of study treatment,
- Sexually active fertile man not using effective birth control during the study and up to 6
months after the last dose of study treatment if his partner is a woman of childbearing
potential.
- ECOG performance status ≥ 2,
- Calculated creatinine clearance < 30 mL/min (Cockcroft-Gault formula),
- Known brain metastasis or leptomeningeal involvement (computed tomography scans
not required to rule this out unless there is clinical suspicion of central nervous system
disease),
- Peripheral neuropathy Grade ≥ 2 by National Cancer Institute Common Toxicity Criteria
[NCI CTC],
- Prior radiation to ≥ 30% of the bone marrow or completed < 30 days ago or without full
recovery of toxicities,
- Other serious concomitant/uncontrolled medical condition including:
o Infection requiring systemic anti-infective therapy within 2 weeks before
randomization or suspected sepsis
o Any medical condition that might not be controlled such as unstable angina,
myocardial infarction within the previous 6 months, unstable congestive heart
failure (NYHA Stage III-IV) or uncontrolled diabetes,
- Electrocardiogram (ECG) with significant modifications suggesting a high risk of
occurrence of an acute clinical event (such as signs of angina pectoris, high risk
arrhythmia, QT/QTc prolongation),
- Prior systemic immunotherapy for advanced or metastatic urothelium carcinoma,
- Prior systemic neoadjuvant/adjuvant chemotherapy that was completed < 6 months
before documented progression,
- Patient who had received any investigational drug within 30 days before randomisation
- History of another malignancy except adequately treated basal carcinoma of the skin, insitu cervix carcinoma, localised prostate cancer with limited risk of recurrence (pT ≤ 2b,
Gleason score ≤ 7) that did not lead to any other treatment apart from prostatectomy, or
any other tumor with a disease free interval ≥ 5 years,
- Patients who require treatment with ketoconazole, itraconazole, ritonavir, amprenavir,
indinavir, rifampicine (any potent CYP3A4 inhibitor or inducer), phenytoine or
medicinal products known to prolong QT/QTc interval,
- Known hypersensitivity to the study drugs or to drugs with similar chemical structures,
- Any previous organ allograft or any chronic system disease requiring concurrent immune
therapy,
- Woman if pregnant or lactating or with positive pregnancy test at inclusion; woman of
child-bearing potential who did not use or is unwilling or unable to use an acceptable
method to avoid pregnancy during the 2 months preceding the start of study treatment,
for the entire study period and for up to 6 months after the last dose of study treatment,
- Sexually active fertile man not using effective birth control during the study and up to 6
months after the last dose of study treatment if his partner is a woman of childbearing
potential.
The Estimated Number of Participants
-
Taiwan
30 participants
-
Global
162 participants
