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Bladder Transitional Cell Carcinoma Stage IVPhase 2JASINT1NCT01599013

JAVLOR Association Study in CDDP-unfit Patients With Advanced Transitional Cell Carcinoma: Gemcitabine Versus Carboplatin

A Phase 2 study testing Vinflunine, Gemcitabine and Vinflunine, Carboplatin in people with Bladder Transitional Cell Carcinoma Stage IV, run by Pierre Fabre Medicament at 1 site in France.

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 is assessing the combination of well known cytotoxics with a novel anti-cancer agent that could be administered as monotherapy without renal toxicity in patients with renal impairment presenting with advanced or metastatic urothelial carcinoma previously treated with a platinum-based regimen. Read more about this study

Who is it for?
Ages 18 to 79 years
What is being tested?
Vinflunine, Gemcitabine and Vinflunine, Carboplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
69 participants
Where
1 siteFrance
Study dates
Feb 2011to Apr 2014
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 to 79 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Man or woman aged ≥ 18 years and < 80 years
  • Signed written informed consent
  • Histologically confirmed diagnosis of locally advanced or metastatic predominantly transitional cell carcinoma of the urothelium (TCCU)
  • Ineligibility for cisplatin-based therapy because of at least one of the following two medical conditions:
  • Calculated creatinine clearance (Cockcroft-Gault formula)< 60 mL/min
  • New York Heart Association Classification Stage II-III Congestive Heart Failure (documented by medical history)
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  • "Measurable" disease with at least one uni-dimensional lesion according to RECIST guideline (version 1.1)
  • ECOG performance status of 0 or 1
  • Estimated life expectancy of at least 12 weeks
  • Patient without prior systemic anticancer therapy unless if it had been administered as neoadjuvant or adjuvant chemotherapy (CT) for TCCU and if the patient has documented relapse ≥ 6 months after the last dose of CT (prior intravesical CT allowed)
  • Adequate bone marrow and hepatic functions as evidenced by:
  • Absolute Neutrophil Count ≥ 2,000/mm3 (≥ 2.0 x 109/L)
  • Haemoglobin ≥ 10 g/dL
  • Platelet count ≥ 100,000/mm3
  • Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • Transaminases ≤ 2.5 x ULN [≤ 5 x ULN only in case of liver metastasis]
  • Absence of psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; these conditions should be assessed with the patient before registration in the trial

Who cannot join

  • ECOG performance status ≥ 2
  • Woman if pregnant or lactating or with positive pregnancy test at inclusion; woman of child-bearing potential who did not use or is unwilling or unable to use an acceptable method to avoid pregnancy during the 2 months preceding the start of study treatment, for the entire study period and for up to 3 months after the last dose of study treatment; sexually active fertile man not using effective birth control during the study and up to 6 months after the last dose of study treatment if his partner is a woman of child-bearing potential
  • Known brain metastasis or leptomeningeal involvement.
  • Peripheral neuropathy Grade ≥ 2 by NCI CTC
  • Prior radiation to ≥ 30% of the bone marrow or completed < 30 days ago or without full recovery of toxicities
  • Other serious illness or medical condition including:
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  • Infection requiring systemic anti-infective therapy
  • Any medical condition that might not be controlled, for instance patients with unstable angina, patients with myocardial infarction within 6 months or uncontrolled diabetes
  • Prior systemic chemotherapy for advanced or metastatic disease or neoadjuvant/adjuvant chemotherapy that was completed < 6 months before documented progression
  • Patient who had received any other investigational drug or anti-cancer therapy within 30 days before randomisation
  • Other malignancies except adequately treated basal carcinoma of the skin, in-situ cervix carcinoma, localised prostate cancer with limited risk of recurrence (pT ≤ 2b, Gleason score ≤ 7) that was incidentally discovered and did not lead to any other treatment apart from prostatectomy, or any other tumor with a disease free interval ≥ 5 years
  • Inadequate renal function defined by a serum creatinine clearance < 30 mL/min (Cockcroft-Gault formula)
  • Known hypersensitivity to the study drugs or to drugs with similar chemical structures
  • Patients who require treatment with ketoconazole, itraconazole, ritonavir, amprenavir, indinavir, rifampicin (any potent CYP3A4 inhibitor or inducer) or phenytoin
  • Any concurrent chronic system immune therapy or previous organ allograft
  • Electrocardiogram (ECG) with significant modifications suggesting a high risk of occurrence of an acute clinical event

Trial locations and contacts

1 site in 1 country.

France1 site

  • Pierre Fabre Research Institute

    Boulogne

Other trials in France

About this study

Official title: Randomized Phase II Study Assessing the Combination of Vinflunine With Gemcitabine and Vinflunine With Carboplatin in Patients Ineligible to Cisplatin With Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium

This study is assessing the combination of well known cytotoxics with a novel anti-cancer agent that could be administered as monotherapy without renal toxicity in patients with renal impairment presenting with advanced or metastatic urothelial carcinoma previously treated with a platinum-based regimen. The intent of this study is to clarify the benefit/risk ratio of the two most promising associations of cytotoxics including the novel therapeutic agent, vinflunine: vinflunine-gemcitabine and vinflunine-carboplatin.

Read the detailed description

Gemcitabine and carboplatin have been the most studied and used anticancer agents in cisplatin-unfit patients with advanced urothelial carcinoma. Both agents previously demonstrated clinical activity as single agent and/or as part of combination regimen in patients with advanced or metastatic disease even if clinical benefits and survival remains limited in this setting for this population.

The purpose of this study is to test in a randomized trial enrolling patients with renal impairment or moderate congestive heart failure two combinations of a novel cytotoxic agent, vinflunine, one with gemcitabine and another with carboplatin in order to determine the most promising combination in the first line treatment of advanced/metastatic urothelial carcinoma.

Being tested
Vinflunine, Gemcitabine, Vinflunine, Carboplatin
Keywords
urothelial carcinoma, bladder cancer, vinflunine, transitional cell carcinoma, advanced or metastatic, unfit, ineligible to cisplatin, renal impairment, renal insufficiency, urologic neoplasms, urogenital neoplasm, urinary neoplasms, cisplatin, tubulin inhibitors
Medical subject headings
Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, Neoplasm Metastasis, Renal Insufficiency, Urologic Neoplasms, Urogenital Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vinflunine, GemcitabineDrug

    Also called JAVLOR, GEMZAR

    • Vinflunine 280 or 250 mg/m2, IV administration over 20 minutes (starting dose based on baseline creatinine clearance value), Day 1 every 3 weeks up to progression or unacceptable toxicity or patient's refusal
    • Gemcitabine 750 or 1000 mg/m2, IV administration over 30 minutes (starting dose based on baseline creatinine clearance value), Day 1 and 8 every 3 weeks up to progression or unacceptable toxicity or patient's refusal

  • Vinflunine, CarboplatinDrug

    Also called JAVLOR, CBDCA

    • Vinflunine 280 or 250 mg/m2, IV administration over 20 minutes (starting dose based on baseline creatinine clearance value), Day 1 every 3 weeks up to progression or unacceptable toxicity or patient's refusal
    • Carboplatin AUC 4.5, IV administration over 60 minutes, Day 1 every 3 weeks up to progression or unacceptable toxicity or patient's refusal
Study groups in NCT01599013
Study groupRoleWhat they receive
Vinflunine plus GemcitabineOtherNot described
Receives: Drug: Vinflunine, Gemcitabine
Vinflunine plus CarboplatinOtherNot described
Receives: Drug: Vinflunine, Carboplatin

What is being measured

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

  1. Disease control rate as defined by RECIST criteria (version 1.1) as a percentage of best overall responses of Complete (CR) + Partial (PR) + Stable Disease (SD) for both Vinflunine-Gemcitabine and Vinflunine-Carboplatin combinations

    Assessment of lesions (measurable and non-measurable) should be performed at baseline and every 6 weeks (assessment interval).

    Evaluable patients: all baseline lesions must have been assessed at least once after the second cycle (6 weeks); patients who progress before the first evaluation will be considered as early progression.

    Primary analysis is planned on the intent to treat population, secondary analysis being performed on the evaluable population.

    Measured: Change from baseline in tumor assessment at 12 weeks (cycle 4)

Secondary outcomes (8)

  1. Tumor Response Rate as defined by RECIST criteria (version 1.1) with a best response as Complete (CR) or Partial (PR)

    Assessment of lesions (measurable and non-measurable) should be performed at baseline and every 6 weeks (assessment interval).

    Evaluable patients: all baseline lesions must have been assessed at least once after the second cycle (6 weeks); patients who progress before the first evaluation will be considered as early progression.

    Measured: Change from baseline in tumor assessment at 12 weeks (cycle 4)

  2. Duration of Disease control in Participants With Best Response of CR + PR + SD

    Tumor assessment at baseline and then every 6 weeks, until tumor progression. Duration of disease control according to investigator will be calculated among the responders and stable patients from the date of randomisation until the documentation of progression or death due to any cause. Patients who are lost to follow-up without progression, or reach the time point of analysis without a known record of progression or death will have the duration of disease control censored at the date of last tumour assessment or last contact of a follow-up showing no progression, whichever occur last.

    Measured: From the date of randomisation until the date of documented progression or date of death due to any cause, assessed up to 10 months

  3. Duration of Response in Participants With Best Response of CR or PR

    Tumor assessment at baseline and then every 6 weeks, until tumor progression. Duration of response will be calculated among the responders (i.e. CR and PR) . Patients who are lost to follow-up, or reach the time point of analysis without a known record of progression or death will have the duration of response censored at the date of last tumour assessment or last contact of a follow-up showing no progression, whichever occur last.

    Measured: From the date that measurement criteria are first met for complete or partial response until the date of documented progression or date of death due to any cause, assessed up to 10 months

  4. Time to First Response calculated among the responders

    Tumor assessment at baseline and then every 6 weeks. Will be calculated among the responders (i.e. CR and PR)

    Measured: From the date of randomisation up to the first report of documented response, assessed up to 12 weeks (cycle 4).

  5. Time to Treatment Failure

    Tumor assessment (RECIST) every 6 weeks. Patients who reach the time point of analysis without failure as defined above will have the time to treatment failure censored at the date of last tumour assessment or last contact of a follow-up not showing progression. Patients who discontinued treatment for other reason and who are lost to follow-up will be censored at the date of last contact.

    Measured: From the date of randomisation until tumor progression, unacceptable toxicity, withdrawal of patient consent, lost to follow-up or start of new anticancer therapy, assessed up to 10 months.

  6. Progression Free Survival

    Tumor assessment every 6 weeks (RECIST).Patients who are lost to follow-up, or reach the time point of analysis without a known record of progression or death will have the progression-free survival censored at the date of last tumour assessment or last contact of a follow-up showing no progression, whichever occur last.

    Measured: From the date of randomisation until the date of progression or the date of death from any cause if no progression was recorded before, median patient follow-up of 11 months

  7. Overall Survival

    Data recording every 3 months. For patients who have not died, survival time will be censored at the date of last news (i.e: date of last administration, tumor assessment, clinical examination, haematological or biochemistrical assessment or date of last contact).

    Measured: From the time of randomisation up to death or last follow-up, assessed with a median patient follow-up of 15 months (assessed up to 24 months)

  8. Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Discontinuation

    Population: all treated patients unless the patient is lost to follow-up immediately after the start of the treatment. The patients will be analysed in the treatment arm they actually received.

    The NCI-CTC classification version 2.0 will be used to classify toxicities. Maximum grade or severity will be reported by cycle and by patient for each MedDRA Preferred Term. Analyses will be performed both regardless the relationship to treatment and related to treatment.

    Biochemical toxicities: the worst CTCAE version 2.0 grade will be analysed according to the grade present at baseline.

    Measured: AE and SAE will be collected up to 30 days after the last treatment administration, on an expected average period of 17 weeks

Timeline

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

  1. First posted15 May 2012 (estimated)
  2. Study startFeb 2011
  3. Primary completionOct 2013
  4. Study completionApr 2014

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
69 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01599013
Sponsor's protocol ID
L00070 IN 213 P1
Acronym
JASINT1
Status last verified
Dec 2015
First submitted
16 Apr 2012
Last updated
8 Dec 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • De Santis M, Wiechno PJ, Bellmunt J, Lucas C, Su WC, Albiges L, Lin CC, Senkus-Konefka E, Flechon A, Mourey L, Necchi A, Loidl WC, Retz MM, Vaissiere N, Culine S. Vinflunine-gemcitabine versus vinflunine-carboplatin as first-line chemotherapy in cisplatin-unfit patients with advanced urothelial carcinoma: results of an international randomized phase II trial (JASINT1). Ann Oncol. 2016 Mar;27(3):449-54. doi: 10.1093/annonc/mdv609. Epub 2015 Dec 16.

    PubMed 26673352

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vinflunine, Gemcitabine and Vinflunine, Carboplatin in people with Bladder Transitional Cell Carcinoma Stage IV, run by Pierre Fabre Medicament at 1 site in France.

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 16 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 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. 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?

Disease control rate as defined by RECIST criteria (version 1.1) as a percentage of best overall responses of Complete (CR) + Partial (PR) + Stable Disease (SD) for both Vinflunine-Gemcitabine and Vinflunine-Carboplatin combinations (time frame: Change from baseline in tumor assessment at 12 weeks (cycle 4)). 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 NCT01599013, 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 Dec 2015.

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