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Urothelial CarcinomaPhase 2VINGEMNCT02665039

A Trial With Vinflunine in Patients With Metastatic Bladder Cancer and Impaired Renal Function

A Phase 2 study testing Vinflunine, Gemcitabine and Carboplatin in people with Urothelial Carcinoma and Bladder Cancer, run by Dr Anders Ullén at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study aim to compare the efficacy, safety and quality of life of vinflunine/gemcitabine and carboplatin/gemcitabine in patients with metastatic urothelial cancer and impaired renal function. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Vinflunine, Gemcitabine and Carboplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
2 sitesin 2 countries
Study dates
Apr 2014to Sep 2018
Phase
Phase 2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed informed consent.
  • Histological or cytological confirmed transitional cell carcinoma of the urothelial tract (mixed histology including transitional cell carcinoma are allowed).
  • Non-curable unresectable (T4b), locally advanced (lymph node positive (N+)) or metastatic (M1) urothelial carcinoma (including renal pelvic tumours, ureteral tumours, urinary bladder tumours and urethral primary tumours).
  • No prior antineoplastic chemotherapy or other anti-cancer drugs. Patients who have received neoadjuvant or adjuvant platinum containing chemotherapy and who are diagnosed with loco regional recurrent or metastatic disease after 6 months are eligible.
  • Creatinine clearance 30 - 60 ml/min (measured by Iohexol or Cr-EDTA technique)
  • ECOG/WHO Performance Status (PS) 0-1.
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  • •≥ 4 weeks since prior major surgery, ≥ 2 weeks since prior minor surgery (i.e. TUR-B) and ≥ 1 week since prior radiation therapy.
  • Measurable and/or non-measurable disease using the RECIST v 1:1 criteria defined as:
  • Measurable disease: lesions that can be measured in at least one dimension and which have not been previously irradiated. Longest diameter ≥10 mm or lymph nodes ≥15 mm in short axis with CT scan or MRI.
  • Non-measurable disease: lesions which have not been previously irradiated, longest diameter <10 mm or lymph nodes 10-14 mm in short axis with CT scan or MRI, or truly non measurable lesions including bone lesions, ascites, pleural/pericardial effusion, and lymphangitis cutis/pulmonitis.
  • CNS metastases and/or leptomeningeal metastases are allowed provided these have been adequately treated with radiotherapy, are stable and not generating any related neurological symptoms.
  • Spinal cord compression due to metastatic lesions is allowed provided adequate surgery and/or radiotherapy has been delivered, the metastases are stable and not generating any related neurological symptoms.
  • No known or suspected allergy to the investigational agents or any agents given in association with this trial.
  • 18 years of age or older.
  • Fertile men and women of childbearing potential must use secure contraception (women - intrauterine devices, hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release), men - condom and for a female partner as described above) from before 2 months entering the study until 6 months after end of chemotherapy.

Who cannot join

  • Not fulfilling inclusion criteria as described above
  • Pure non-transitional cell carcinoma of the urothelial.
  • Pronounced hematuria in need of repeated blood transfusions, palliative radiotherapy to the bladder or palliative resection (TUR-B).
  • Impaired bone marrow function defined as WBC < 3.0 x 109/L, neutrophils < 1.5 x 109/L, platelets < 125 x 109/L, haemoglobin < 100 g/L.
  • Impaired liver function defined as serum bilirubin > 1.5 x upper limit of normal (ULN) and/or ASAT/ALAT > 2.5 x ULN (> 5 x ULN if known liver metastasis).
  • Electrocardiogram (ECG) with significant modifications suggesting a high risk of occurrence of angina pectoris or high risk of arrhythmia.
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  • Other malignancies, except adequately treated basal carcinoma or squamous cell 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.
  • History of serious or concurrent illness or uncontrolled medical disorder; any medical condition that might be aggravated by chemotherapy treatment or which could not be controlled; including, but not restricted to:
  • Active infection requiring antibiotics within 2 weeks before the study inclusion,
  • Unstable diabetes mellitus,
  • Hypercalcaemia >2.9 mmol/L (grade ≥ 2 according to CTCAE v 4.0),
  • Concurrent congestive heart failure NYHA (class III-IV),
  • Unstable angina pectoris, or myocardial infarction within 6 months and/or poorly controlled hypertension,
  • QTc > 450 ms at baseline,
  • Inflammatory bowel disease,
  • Peripheral neuropathy grade ≥ 2 according to CTCAE v 4.0,
  • Patients who require treatment with ketoconazole, fluconazole, itraconazole, ritonavir, amprenavir, indinavir, rifampicin (any potent CYP3A4 inhibitor or inducer) or phenytoin.
  • Pregnant or lactating women.
  • Any psychological, familial, sociological, or geographical condition which does not permit protocol compliance and medical follow-up.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Denmark1 site

  • Department of Oncology, Rigshospitalet

    Copenhagen, DK-2100

Other trials in Denmark

Sweden1 site

  • Department of Oncology, Karolinska University Hospital

    Stockholm

Other trials in Sweden

About this study

Official title: A Multicenter, Randomized Phase II Trial of Vinflunine/Gemcitabine vs Carboplatin/Gemcitabine as First Line Treatment in Patients With Metastatic Urothelial Carcinoma Unfit for Cisplatin Based Chemotherapy Due to Impaired Renal Function.

This study aim to compare the efficacy, safety and quality of life of vinflunine/gemcitabine and carboplatin/gemcitabine in patients with metastatic urothelial cancer and impaired renal function.

Read the detailed description

Rational The standard first line treatment for patients with metastatic urothelial carcinoma unfit for cisplatin due to renal impairment is carboplatin containing chemotherapy, with a median overall survival of approximately 8-10 month. New, more effective regimens in terms of tumor control and quality of life are urgently needed. Vinflunine has proven efficacy in urothelial carcinoma and is registered as second line treatment. The combination of gemcitabine and vinflunine has not yet been evaluated in first line treatment for patients with metastatic urothelial carcinoma.

Objectives

  • To compare the progression free survival (FPS) of vinflunine/gemcitabine versus carboplatin/gemcitabine in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract unfit for cisplatin based chemotherapy due to impaired renal function.
  • To evaluate the tumour response (ORR), overall survival (OS) and disease control rate (DCR) of vinflunine/gemcitabine versus carboplatin/gemcitabine
  • To assess the safety and toxicity of vinflunine/gemcitabine versus carboplatin/gemcitabine.
  • To investigate and compare Quality of life during treatment with vinflunine/gemcitabine and carboplatin/gemcitabine respectively.
Being tested
Vinflunine, Gemcitabine, Carboplatin
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 will be given intravenously once every 21 days, starting at a dose of:

    • 280 mg/m2 in patients with GFR 40-60 ml/min
    • 250 mg/m2 in patients aged >80 years and/or GFR 30-40 ml/min

  • GemcitabineDrug

    Also called Gemzar

    Gemcitabine will be given intravenously on day 1 and day 8 of every 21 day cycle, starting at a dose of 1000 mg/m2

  • CarboplatinDrug

    Also called Karboplatin

    Carboplatin will be given intravenously once every 21 days, starting at a dose of AUC 4.5

Study groups in NCT02665039
Study groupRoleWhat they receive
Vinflunine + gemcitabineExperimentalVinflunine will be given intravenously once every 21 days, starting at a dose of: * 280 mg/m2 in patients with GFR 40-60 ml/min * 250 mg/m2 in patients aged >80 years and/or GFR 30-40 ml/min Gemcitabine will be given intravenously on day 1 and day 8 of every 21 day cycle, starting at a dose of 1000 mg/m2
Receives: Drug: Vinflunine; Drug: Gemcitabine
Carboplatin + gemcitabineActive comparatorCarboplatin will be given intravenously once every 21 days, starting at a dose of AUC 4.5 Gemcitabine will be given intravenously on day 1 and day 8 of every 21 day cycle, starting at a dose of 1000 mg/m2
Receives: Drug: Gemcitabine; Drug: Carboplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival (PFS)

    Defined as the duration from randomization to either confirmed progression (by RECIST) or death from any cause.

    Measured: From randomization through study completion, on average within 9 months

Secondary outcomes (5)

  1. Overall response rate (ORR = CR + PR)

    Defined as best confirmed response according to RECIST through study completion from randomization to either confirmed progression (by RECIST) or death from any cause

    Measured: From randomization through study completion, on average within 9 months

  2. Overall survival (OS)

    Defined as the duration from randomization to death from any cause or last follow-up.

    Measured: From randomization to death from any cause, on average within 18 months

  3. Disease control rate, DCR (=CR + PR + SD)

    Defined as the percentage of patients who have achieved complete response, partial response and stable disease according to RECIST through study completion from randomization to either confirmed progression (by RECIST) or death from any cause

    Measured: From randomization through study completion, on average within 9 months

  4. Number of patients with treatment-related adverse events as assessed by CTCAE v4.0

    Treatment-related adverse events will be assessed by CTCAE v4.0. The safety profile and tolerability of vinflunine + gemcitabine compared to carboplatin + gemcitabine will be determined from the number of Adverse Events reported.

    Measured: From the date the informed consent is signed up to 30 days after the last dose

  5. Quality of Life (QoL) assessed by QLQ-C30

    Quality of Life will be assessed by the EORTC Quality of Life Questionnaire C30 (QLQ-C30) Version 3.0. The QoL for patients treated with vinflunine + gemcitabine will be compared to patients treated with carboplatin + gemcitabine

    Measured: From the date the informed consent is signed up to 30 days after the last dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2016 (estimated)
  2. Study startApr 2014
  3. Primary completionSep 2018
  4. Study completionSep 2018

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02665039
Sponsor's protocol ID
NUCOG I
Acronym
VINGEM
Status last verified
Oct 2019
First submitted
18 Jan 2016
Last updated
8 Oct 2019
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Holmsten K, Jensen NV, Mouritsen LS, Jonsson E, Mellnert C, Agerbaek M, Nilsson C, Moe M, Carus A, Ofverholm E, Lahdenpera O, Brandberg Y, Johansson H, Hellstrom M, Maase HV, Pappot H, Ullen A. Vinflunine/gemcitabine versus carboplatin/gemcitabine as first-line treatment in cisplatin-ineligible patients with advanced urothelial carcinoma: A randomised phase II trial (VINGEM). Eur J Cancer. 2020 Mar;127:173-182. doi: 10.1016/j.ejca.2019.08.033. Epub 2019 Oct 22.

    PubMed 31648851

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vinflunine, Gemcitabine and Carboplatin in people with Urothelial Carcinoma and Bladder Cancer, run by Dr Anders Ullén at 2 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 15 inclusion and 19 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 8 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Progression-free survival (PFS) (time frame: From randomization through study completion, on average within 9 months). 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 NCT02665039, 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 8 Oct 2019.

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