Urothelial CarcinomaPhase 1VINSORNCT01844947
Phase I Study With Sorafenib in Addition to Vinflunine in Metastatic Transitional Cell Carcinoma of the Urothelial Tract
A Phase 1 study testing Vinflunine and Sorafenib in people with Urothelial Carcinoma and Bladder Cancer, run by Dr Anders Ullén at 3 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Urothelial Carcinoma, Bladder Cancer, Renal Pelvis Cancer
- What is being tested?
- Vinflunine and Sorafenib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 3 sitesin 2 countries
- Study dates
- May 2012to 5 Jun 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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;
Who cannot join
- 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;
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- 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
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Denmark2 sites
Department of Oncology, Aarhus University Hospital
Aarhus, DK-8200
Department of Oncology, Rigshospitalet
Copenhagen, DK-2100
Sweden1 site
Department of Oncology, Karolinska University Hospital
Stockholm, SE-171 76
About this study
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
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.
Read the 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.
- Being tested
- Vinflunine, Sorafenib
- Medical subject headings
- Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, Ureteral Neoplasms, Urethral Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VinflunineDrug
Also called Javlor
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.
SorafenibDrug
Also called Nexavar
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.
| Study group | Role | What they receive |
|---|---|---|
| vinflunine + sorafenib | Experimental | Single arm study. Receives: Drug: Vinflunine; Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2013 (estimated)
- Study startMay 2012
- Primary completion18 Oct 2017
- Study completion5 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Urothelial CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr Anders Ullén
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer, Pierre Fabre Laboratories, Nordic Urothelial Cancer Oncology Group
- Responsible party
- Sponsor-investigator, Dr Anders Ullén, Karolinska University Hospital
- Investigators
- Anders Ullén, M.D., Ph.D., Principal investigator, Dept of Oncology, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01844947
- Sponsor's protocol ID
- NUCOG III
- Other IDs
- 2011-004289-14
- Acronym
- VINSOR
- Status last verified
- Apr 2019
- First submitted
- 5 Nov 2012
- Last updated
- 26 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 30552156
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01844947
- Acronym / sponsor ID
- VINSOR / NUCOG III
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Dr Anders UllénUniversity, hospital or other
- Collaborators
- Bayer, Pierre Fabre Laboratories, Nordic Urothelial Cancer Oncology Group
- Study start
- May 2012 (actual)
- Primary completion
- 18 Oct 2017 (actual)
- Study completion
- 5 Jun 2018 (actual)
- First posted
- 3 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| vinflunine + sorafenib | Experimental | Drug: Vinflunine, Drug: SorafenibSingle arm study. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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;
Key exclusion criteria (17 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VinflunineAlso: JavlorVinflunine (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. | Drug | vinflunine + sorafenib |
| SorafenibAlso: NexavarSorafenib (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. | Drug | vinflunine + sorafenib |
Primary outcome
Number of patients with adverse events
Time frame: 6 weeks
Primary endpoint: Define the recommended phase II dose (RPTD) by the number of dose limiting toxicity events (recorded during treatment cycle 1 and 2)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2019.
- Derived from this study: PubMed 30552156Shah 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anders Ullén, M.D., Ph.D. principal investigator
Dept of Oncology, Karolinska University Hospital
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vinflunine and Sorafenib in people with Urothelial Carcinoma and Bladder Cancer, run by Dr Anders Ullén at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Denmark, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with adverse events (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01844947, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2019.