Brief Title
Phase I Study With Sorafenib in Addition to Vinflunine in Metastatic Transitional Cell Carcinoma of the Urothelial Tract
Official Title
An Exploratory Phase I Study With Sorafenib in Addition to Vinflunine in Progressive Locally Advanced or Metastatic Transitional Cell Carcinoma of the Urothelial Tract
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.
Detailed 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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Number of patients with adverse events
Condition
Urothelial Carcinoma
Intervention
Vinflunine
Study Arms / Comparison Groups
vinflunine + sorafenib
Description: Single arm study.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
22
Start Date
May 2012
Completion Date
June 5, 2018
Primary Completion Date
October 18, 2017
Eligibility Criteria
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 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
Gender
All
Ages
18 Years - 80 Years
Accepts Healthy Volunteers
No
Contacts
Anders Ullén, M.D., Ph.D., ,
Location Countries
Denmark
Location Countries
Denmark
Administrative Informations
NCT ID
NCT01844947
Organization ID
NUCOG III
Secondary IDs
2011-004289-14
Responsible Party
Sponsor-Investigator
Study Sponsor
Dr Anders Ullén
Collaborators
Bayer
Study Sponsor
Anders Ullén, M.D., Ph.D., Principal Investigator, Dept of Oncology, Karolinska University Hospital
Verification Date
April 2019