- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01265940
Pazopanib and Vinflunine in Urothelial Cancer of the Bladder
Target-specific Therapy With Pazopanib as Add-on to Vinflunine in Patients With Advanced or Metastatic Urothelial Carcinoma of the Bladder After Failure of Platinum-based Treatment
Urothelial carcinoma of the bladder mostly is chemically induced and represents the second prevalent urooncological disease. About 20% of newly diagnosed urothelial carcinoma cases of the bladder are already advanced or metastasized. Before 2008 2009 no second line therapy after failure of primary systemic therapy of advanced / metastatic disease was established outside of clinical trials. The actual standard for this situation was a supportive, symptomatic therapy. Vinflunine has demonstrated improved survival from 4.3 to 6.9 months (p=0.04), with an adequate disease control, good symptom control and with acceptable toxicity. Based on these results, this compound became standard se¬cond line treatment for refractory metastatic bladder cancer disease after failure of platinum-containing therapy. As the prognosis still remains poor, new treatment opportunities have to be explored.
The target-specific therapy with Pazopanib suggests a positive influence of both inductive and perioperative treatment of solid tumors. Pazopanib has been approved by the FDA and the EMA for the treatment of advance renal cell carcinoma. Results for advanced urothelial carcinoma are missing so far as well as data on tolerability of the combination of both vinflunine and pazopanib. As the pharmacodynamic properties as well as the safety profile of both drugs are different, assumption is justified that there might occur additive efficacy effects without addition of adverse outcomes. Aim of the study thus is
- To define the maximum tolerated dose (MTD) of Pazopanib in combination with Vinflunine in a phase-I-setting and
- To further assess efficacy and safety of the combination at the MTD level in phase II.
During the pase-I-part of the study different doses of pazopanib will be added to the standard vinflunine scheme in groups of 6 patients maximum. Dose escalation will only be performed in the next patient group if not more than one out of six patients shows dose-limiting toxicity. Each patient will be treated with the drug combination for a duration of two vinflunine cycles, that is six weeks.
During the phase-II study new patients will be treated with the drug combination at maximum-tolerated dose until disease progression (assessed by RECIST 1.1 procedures).
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Neuss, Germany, 41464
- Lukaskrankenhaus
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Written informed consent
- Age ≥ 18 years
- Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) with lymphatic (N-stage 2-3) and/or distant metastases (M-stage 1) not amenable to definitive regional/local therapy
- Progression of tumor disease after platinum containing systemic chemotherapy for advanced or metastatic disease
- Eastern Cooperative Oncology Group (ECOG) performance status of 1
- estimated minimal life expectancy of 3 months at screening
- At least one measurable tumor lesion according to RECIST 1.1 criteria
- Adequate organ system function at screening
- Adequate contraception
Exclusion Criteria:
- More than 1 prior chemotherapy, biologic therapy or hormonal therapy within 14 days prior to the first dose of study medication
- Prior malignancy within 5 years prior to inclusion (exception: successfully treated basal cell carcinoma or in situ carcinoma)
- History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis
Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding within 28 days prior to beginning study treatment, e.g
- Active peptic ulcer disease
- Known intraluminal metastatic lesion/s with risk of bleeding
- Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation
- History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess
Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product, e.g.
- Malabsorption syndrome
- Major resection of the stomach or small bowel
- Active infection requiring antibiotics within 14 days before registration
- Corrected QT interval (QTc) > 480 msecs using Bazett's formula at screening
- Screening-electrocardiogram (ECG) with any significant modifi¬cations suggesting a high risk of occurrence of an acute clinical event (such as signs of angina pectoris, high risk arrhythmia etc.)
History of one or more of the following cardiac / cardiovascular conditions within the past 6 months before registration:
- Cardiac angioplasty or stenting
- Myocardial infarction
- Unstable angina
- Coronary artery bypass graft surgery
- Symptomatic peripheral vascular disease
- NYHA Class II, III or IV congestive heart failure
- Uncontrolled cardiac arrhythmia
- Poorly controlled hypertension, defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90 mmHg
- History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months before registration
- Peripheral neuropathy grade ≥ 2 (NCI CTC v3.0)
- Unstable diabetes mellitus
- Uncontrolled hypercalcaemia > 2.9 mmol/L
- Prior major surgery or trauma within 28 days prior to registration and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major)
- Evidence of active bleeding e.g. GI bleeding or bleeding diathesis at screening.
- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
- Hemoptysis with bleeding of > 2.5 mL within 8 weeks before registration
- Any serious and/or unstable pre-existing medical, psychiatric/psychological, familial, sociological, geographical or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
- prior to the first dose of study drug and for the duration of the study
- Radiation, surgery or tumor embolization or any investigational treatment within 14 days prior to the first dose of study medication
- Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or progressing in severity, except nausea, vomiting, alopecia
- ASA 4
- Pre-treatment with Pazopanib or Vinflunine
- Pregnancy or lactation
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Pazopanib + Vinflunine
|
Patients will receive vinflunine standard regimen (intravenous infusion every three weeks) as specified per drug label plus additional pazopanib as daily oral medication. Doses of pazopanib will be escalated in 200 mg/d steps during phase I up to a maximum of 800 mg/d. In Phase II the patients will be given pazopanib + vinflunine at maximum tolerated dose.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I: Definition of the Maximum Tolerated Dose (MTD) of Pazopanib in combination with Vinflunine.
Time Frame: 6 weeks (two cycles of vinflunine)
|
MTD ist defined as the dose level with dose-limiting toxicity occurring in maximum one out of six patients.
|
6 weeks (two cycles of vinflunine)
|
Phase II: Progression-free survival rate
Time Frame: 3 months
|
Progression-free survival will be assessed by means of RECIST 1.1.
methodology
|
3 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I: Progression-free survival rate, Phase II: Safety profile, overall survival
Time Frame: Six weeks after first administration of study drug.
|
Progression-free survival will be assessed by means of RECIST 1.1.
methodology
|
Six weeks after first administration of study drug.
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Urologic Diseases
- Urinary Bladder Diseases
- Urinary Bladder Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Vinblastine
Other Study ID Numbers
- DZITM1
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Advanced Urothelial Cancer of Bladder After Failure of Platinum-containing Therapy.
-
xCuresTerminatedTransitional Cell Carcinoma | Bladder Cancer | Urothelial Carcinoma | Metastatic Urothelial Carcinoma | FGFR2 Gene Mutation | FGFR3 Gene Mutation | FGFR2 Amplification | Bladder Urothelial Carcinoma | Locally Advanced Urothelial Carcinoma | Refractory Bladder Carcinoma | Refractory Bladder Urothelial Carcinoma and other conditionsUnited States
-
University of California, DavisMerck Sharp & Dohme LLCCompletedRecurrent Bladder Carcinoma | Stage III Urethral Cancer | Stage IV Urethral Cancer | Urethral Urothelial Carcinoma | Stage IV Bladder Urothelial Carcinoma | Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter | Stage III Bladder Urothelial Carcinoma | Recurrent Urothelial Carcinoma of... and other conditionsUnited States
-
Memorial Sloan Kettering Cancer CenterAstraZenecaCompletedAdenocarcinoma of the Bladder | Squamous Cell Carcinoma of the Bladder | Metastatic Bladder Cancer | Non-Transitional Cell Carcinoma of the Urothelial Tract | Small Cell of the BladderUnited States
-
Fox Chase Cancer CenterCompletedMuscle Invasive Bladder Cancer | High Risk Urothelial Carcinoma of the Upper Urinary TractsUnited States
-
IRCCS San RaffaeleRecruitingBladder Cancer | Bladder Disease | Bladder Cancer Recurrent | Bladder Urothelial Carcinoma | Non Muscle Invasive Bladder Cancer | Bladder Neoplasm | Non-Muscle Invasive Bladder Urothelial Carcinoma | Non-Muscle Invasive Bladder Neoplasms | Bladder Cancer Stage I, With Cancer in Situ | Bladder Urothelial... and other conditionsItaly
-
Dana-Farber Cancer InstituteGilead SciencesActive, not recruitingBladder Cancer | Urothelial Cancer | Metastatic Urothelial Carcinoma | Metastatic Urothelial Carcinoma of the Renal Pelvis and UreterUnited States
-
NYU Langone HealthMerck Sharp & Dohme LLCActive, not recruitingMuscle-invasive Urothelial Cancer of the BladderUnited States
-
Vaxiion TherapeuticsCompletedUrothelial Carcinoma of the Urinary BladderUnited States
-
SignPath Pharma, Inc.CompletedPatients w/Advanced Cancer That Failed Std of Care TherapyAustria
-
NanOlogy, LLCUS Biotest, Inc.CompletedUrologic Neoplasms | Urogenital Neoplasms | Urinary Bladder Cancer | Bladder Cancer | Urothelial Carcinoma | Urologic Cancer | Urinary Bladder Neoplasm | Cancer of the Bladder | Malignant Tumor of the Urinary BladderUnited States
Clinical Trials on Pazopanib as add-on to vinflunine
-
Central Institute of Mental Health, MannheimRecruiting
-
University of AarhusTerminated
-
Rigshospitalet, DenmarkUniversity College CopenhagenNot yet recruitingPost-Concussion Syndrome
-
SOTIO a.s.CompletedStage IV Non-small Cell Lung CancerCzechia, Slovakia
-
InxMed (Shanghai) Co., Ltd.RecruitingPlatinum-resistant Ovarian CancerChina
-
KeyBioscience AGNordic Bioscience A/SCompletedType 2 Diabetes MellitusDenmark, Czechia, Poland, Moldova, Republic of, Romania, United Kingdom
-
National Institute of Diabetes and Digestive and...CompletedHypertensive Renal DiseaseUnited States
-
Shiga UniversityOsaka University; Kanazawa Medical University; Nagahama Red Cross Hospital; Nagahama... and other collaboratorsUnknownType 2 Diabetes MellitusJapan
-
Vanderbilt University Medical CenterNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)CompletedType 2 DiabetesUnited States
-
University of AlbertaRecruitingGeneralized Anxiety Disorder | Major Depressive Disorder | Pharmacist-Patient RelationsCanada