NCT01844947

Brief 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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
22

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started May 2012

Longer than P75 for phase_1

Geographic Reach
2 countries

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2012

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

November 5, 2012

Completed
6 months until next milestone

First Posted

Study publicly available on registry

May 3, 2013

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 18, 2017

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 5, 2018

Completed
Last Updated

April 26, 2019

Status Verified

April 1, 2019

Enrollment Period

5.5 years

First QC Date

November 5, 2012

Last Update Submit

April 25, 2019

Conditions

Urothelial CarcinomaBladder CancerRenal Pelvis CancerUreter CancerUrethra Cancer

Outcome Measures

Primary Outcomes (1)

  • 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

Study Arms (1)

vinflunine + sorafenib

EXPERIMENTAL

Single arm study.

Drug: VinflunineDrug: Sorafenib

Interventions

VinflunineDRUG

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.

Also known as: Javlor
vinflunine + sorafenib
SorafenibDRUG

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.

Also known as: Nexavar
vinflunine + sorafenib

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Department of Oncology, Aarhus University Hospital

Aarhus, DK-8200, Denmark

Location

Department of Oncology, Rigshospitalet

Copenhagen, DK-2100, Denmark

Location

Department of Oncology, Karolinska University Hospital

Stockholm, SE-171 76, Sweden

Location

Related Publications (1)

  • Shah CH, Pappot H, Agerbaek M, Holmsten K, Jaderling F, Yachnin J, Gryback P, von der Maase H, Ullen A. Safety and Activity of Sorafenib in Addition to Vinflunine in Post-Platinum Metastatic Urothelial Carcinoma (Vinsor): Phase I Trial. Oncologist. 2019 Jun;24(6):745-e213. doi: 10.1634/theoncologist.2018-0795. Epub 2018 Dec 14.

    PMID: 30552156DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional CellUrinary Bladder NeoplasmsUreteral NeoplasmsUrethral Neoplasms

Interventions

vinflunineSorafenib

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsUrologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesUrinary Bladder DiseasesUrologic DiseasesMale Urogenital DiseasesUreteral DiseasesUrethral Diseases

Intervention Hierarchy (Ancestors)

Phenylurea CompoundsUreaAmidesOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsNiacinamideNicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Anders Ullén, M.D., Ph.D.

    Dept of Oncology, Karolinska University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Associate Professor/Sr Consultant Clinical Oncology

Study Record Dates

First Submitted

November 5, 2012

First Posted

May 3, 2013

Study Start

May 1, 2012

Primary Completion

October 18, 2017

Study Completion

June 5, 2018

Last Updated

April 26, 2019

Record last verified: 2019-04

Data Sharing

IPD Sharing
Will not share

Locations

DK(2)SE(1)