Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01844947
Other study ID # NUCOG III
Secondary ID 2011-004289-14
Status Completed
Phase Phase 1
First received
Last updated
Start date May 2012
Est. completion date June 5, 2018

Study information

Verified date April 2019
Source Karolinska University Hospital
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study aims to analyse the tolerability (side effects and safety) with standard treatment (Javlor®) with the addition of a second anti-tumour drug: sorafenib (Nexavar®). This is the first time this treatment combination is studied in humans. Samples of blood, urine and tumour tissues will be analysed for molecular biomarkers. These biomarkers may potentially help us in the future in predicting whether a patient will benefit or not from the cancer treatment. The study also aims to investigate if a newer imaging method, called PET-CT (positron emission tomography-computed tomography), at an earlier stage (than a normal CT scan) can identify patients who will benefit from the given treatment.


Description:

Objectives

- To explore the safety of sorafenib in combination with vinflunine in patients with transitional cell carcinoma of the urothelial tract and to define a recommended phase II dose for this treatment combination

- To correlate early tracer 18F-FDG-PET/CT functional imaging readouts with standard RECIST (version 1.1) evaluations with the intention to explore new endpoints for targeted therapy

- To find predictive tumour tissue biomarkers for sorafenib/vinflunine treatment

- To evaluate serum and urine markers of apoptosis as potential markers of sorafenib/vinflunine treatment

Rationale/Goal

To evaluate the tolerability and activity of sorafenib combined with vinflunine in patients with advanced or metastatic urothelial cancer.

Tumour biopsies will be collected before and after one cycle of therapy. The translational part of this study aims to explore the predictive value of a number of biomarkers related to the targeted properties of sorafenib and presumptive markers for vinflunine treatment.

In addition, the predictive value of an early functional imaging tracer 18F-FDG-PET/CT will be evaluated.


Recruitment information / eligibility

Status Completed
Enrollment 22
Est. completion date June 5, 2018
Est. primary completion date October 18, 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility Inclusion Criteria:

- signed informed consent;

- histologically confirmed transitional cell (pure or mixed histology including transitional cell carcinoma are allowed) carcinoma of the urothelial tract;

- patients who have received neoadjuvant or adjuvant platinum-containing chemotherapy and who are diagnosed with locoregional recurrent or metastatic disease prior to or at the 6-months? visit , are eligible or

- patients who have received palliative platinum-containing chemotherapy and who are diagnosed with progression prior to or at the 6-months? visit, are eligible or

- patients who have contraindication to platinum-containing chemotherapy;

- previous systemic chemotherapy must have been stopped 14 days before the inclusion with recovery (G1 or less) from any treatment related toxicity;

- measurable and/or non-measurable disease using RECIST and defined as: Measurable disease: lesions that can be measured in at least one dimension and which have not been previously irradiated. Longest diameter 20 mm with conventional techniques or 10 mm with spiral CT scan or MRI. Non-measurable disease: lesions which have not been previously irradiated, or longest diameter <20 mm with conventional techniques or <10 mm with spiral CT scan or MRI, or truly non measurable lesions including bone lesions, ascites, pleural/pericardial effusion, and lymphangitis cutis/pulmonitis;

- age 18 up to 80 years;

- ECOG / WHO Performance Status (PS) =1;

- haematological function: haemoglobin =100 g/L absolute neutrophil count 1.0 x LL (lower limit of normal value) platelets 100 x 109/L;

- hepatic function: bilirubin <1.5 x ULN*, transaminases <2.5 x ULN*

*ULN = upper limit of normal value

- renal function: creatinine clearance 40 ml/min (measured by either iohexol clearance or Cr-EDTA technique);

- Clinically normal cardiac function based on ejection fraction (LVEF assessed by MUGA or ECHO, LVEF =50%);

- able to swallow and retain oral medication;

- previous treatment related toxicity must be grade =1 at time of inclusion and no presence of asthenia, hand-foot skin reaction or rash grade >1 (NCI CTCAE v4.0) at enrolment;

- no known or suspected allergy to the investigational agent or any agents given in association with this trial;

Exclusion Criteria:

- non-transitional cell carcinoma of the urothelial tract (e.g. pure adenocarcinoma or squamous cell carcinoma);

- prior treatment with vinflunine;

- diagnosed brain metastases or leptomeningeal involvement. Brain CT-scans or MRI are not required unless there is clinical suspicion of central nervous system involvement.

- peripheral neuropathy G3 (NCI CTCAE v4.0);

- history of serious or concurrent illness or uncontrolled medical disorder; any medical condition that might be aggravated by treatment or which could not be controlled: active infection requiring antibiotics within 2 weeks before the study inclusion, unstable diabetes mellitus, uncontrolled hypercalcaemia >2.9 mmol/L (or >G2 NCI CTCAE v4.0), concurrent congestive heart failure NYHA (class III-IV) or any type of angina pectoris and/or a diagnosis of myocardial infarction during the previous 6 months and/or poorly controlled hypertension will be excluded, QTc >450 ms at baseline, additional risk factors for Torsade de Pointes (heart failure and hypokalemia (=G1, i.e. P-K <LLN-2.5 mM) or family history of long QT-syndrome), cardiac arrhythmias requiring anti-arrhythmics (excluding beta-blockers or digoxin for chronic atrial fibrillation);

- patients having received more than one previous systemic chemotherapy for advanced or metastatic disease;

- patients who have received any other investigational or anti-cancer therapy 14 days before the inclusion;

- other malignancies, except adequately treated basal carcinoma of the skin or in-situ cervix carcinoma or incidental prostate cancer (T1a, Gleason score =6, PSA <0.5 ng/ml), or any other tumour with a disease free survival of =5 years;

- pregnant or lactating women;

- men or women of childbearing potential not employing adequate contraception;

- any psychological, familial, sociological, or geographical condition which does not permit protocol compliance and medical follow-up.

- poorly controlled hypertension. At baseline, blood pressure >150/90 is defined as poorly controlled.

- renal dysfunction: creatinine clearance <40 ml/min measured by either iohexol clearance or Cr-EDTA technique.

- ECOG / WHO Performance Status =2

- presence of hand-foot skin reaction or rash >G1 at enrolment;

- known or suspected allergy to the investigational agent or any agents given in association with this trial;

- current medical treatment with any compound that prolongs QTc

Study Design


Intervention

Drug:
Vinflunine
Vinflunine (Javlor®, Pierre Fabre Pharma): 320 mg/m2 I.V., day 1, repeated every 21 days for patients with PS 0, adequate renal (creatinine clearance >60 ml/min) and hepatic function (as described in the inclusion criteria). PLEASE NOTE THAT THE 320 mg/m2 ARM IS CLOSED FOR RECRUITMENT. For patients with PS 1, or age 75 to 80 years, or exposed to radiation of the lower pelvis region, or with impaired renal function (creatinine clearance 40-60 ml/min) but adequate hepatic function (as described in the inclusion criteria), the dose of vinflunine is 280 mg/m2 I.V. day 1, repeated every 21 days.
Sorafenib
Sorafenib (Nexavar®, Bayer HealthCare) daily dosage from day 2 through day 21 (repeated every 21 days): Step 1: 400 mg P.O. (i.e. one (1) tablet 200 mg morning and evening, 1+0+1) Step 2: 600 P.O. (i.e. one (1) tablet 200 mg morning and two tablets evening, 1+0+2) Step 3: 800 mg P.O. (i.e. two (2) tablets 200 mg morning and evening, 2+0+2) Doses of sorafenib higher than 400 mg P.O. b.i.d. are not allowed.

Locations

Country Name City State
Denmark Department of Oncology, Aarhus University Hospital Aarhus
Denmark Department of Oncology, Rigshospitalet Copenhagen
Sweden Department of Oncology, Karolinska University Hospital Stockholm

Sponsors (4)

Lead Sponsor Collaborator
Dr Anders Ullén Bayer, Nordic Urothelial Cancer Oncology Group, Pierre Fabre Laboratories

Countries where clinical trial is conducted

Denmark,  Sweden, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of patients with adverse events Primary endpoint:
Define the recommended phase II dose (RPTD) by the number of dose limiting toxicity events (recorded during treatment cycle 1 and 2)
6 weeks
See also
  Status Clinical Trial Phase
Not yet recruiting NCT06034015 - A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of APL-1501 Extended Release (ER) Capsules Compared to APL-1202 Immediate Release (IR) Tablets in Healthy Volunteers Phase 1
Recruiting NCT04235764 - En-bloc Transurethral Resection of Bladder Tumor (En-bloc TURBT) Specimens Using a Redesigned Surgical Resectoscope Device
Completed NCT02371447 - VPM1002BC in Recurrent Non-muscle Invasive Bladder Cancer Phase 1/Phase 2
Recruiting NCT04081246 - Transurethral Modified En Bloc Resection For Large Bladder Tumours. N/A
Recruiting NCT06059547 - Neoadjuvant Immunotherapy in Combination With the Anti-GDF-15 Antibody Visugromab (CTL-002) for Treatment of Muscle Invasive Bladder Cancer Phase 2
Terminated NCT04779489 - Checkpoint Inhibitor and Radiation Therapy in Bulky, Node-Positive Bladder Cancer N/A
Not yet recruiting NCT04493489 - Propranolol Adjuvant Treatment of Bladder Cancer Phase 2
Completed NCT03520231 - Study Comparing Denosumab With Standard Treatment in Urothelial Cancer Patients With Bone Metastases Phase 2
Recruiting NCT04537221 - Nordic Cystectomy Study III - Transfusion
Withdrawn NCT03007771 - Magnetic Resonance-guided High-Intensity Focused Ultrasound (MR-HIFU) Used for Mild Hyperthermia Phase 1
Completed NCT01955408 - Severity of Overactive Bladder Symptoms in Patients After Synergo Treatment N/A
Completed NCT04487457 - Prospective Study to Evaluate the Blood Kinetics of Immune Cells and Immunosuppressive Cytokines After Exposure to an Immunity Checkpoint Inhibitor (ICI): Study of the Impact of Chemotherapy
Active, not recruiting NCT04383210 - Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors Phase 2
Recruiting NCT05562791 - A Study of 68Gallium PSMA-PET/CT Scans in People With Bladder Cancer Phase 1
Completed NCT00199849 - NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine Phase 1
Completed NCT02781428 - To Detect the Sensitivity of the UroMark Assay
Recruiting NCT04738630 - Study of HX008 for the Treatment of BCG-Unresponsive Non-muscle Invasive Bladder Cancer Phase 2
Completed NCT03980041 - Study to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275) Phase 2
Active, not recruiting NCT03978624 - Window of Opportunity Study of Pembrolizumab Alone and in Combinations in Bladder Cancer Phase 2
Completed NCT04534309 - Behavioral Weight Loss Program for Cancer Survivors in Maryland N/A