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

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ClinicalTrials.gov Identifier: NCT02665039
Recruitment Status : Active, not recruiting
First Posted : January 27, 2016
Last Update Posted : March 8, 2018
Sponsor:
Information provided by (Responsible Party):
Dr Anders Ullén, Karolinska University Hospital

Brief 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.

Condition or disease Intervention/treatment Phase
Urothelial Carcinoma Bladder Cancer Renal Pelvis Cancer Ureter Cancer Urethra Cancer Drug: Vinflunine Drug: Gemcitabine Drug: Carboplatin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Study Start Date : April 2014
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : January 2019


Arm Intervention/treatment
Experimental: Vinflunine + gemcitabine

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

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

Drug: Vinflunine

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
Other Name: Javlor®

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

Active Comparator: Carboplatin + gemcitabine

Carboplatin 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

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

Drug: Carboplatin
Carboplatin will be given intravenously once every 21 days, starting at a dose of AUC 4.5
Other Name: Karboplatin




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: From randomization through study completion, on average within 9 months ]
    Defined as the duration from randomization to either confirmed progression (by RECIST) or death from any cause.


Secondary Outcome Measures :
  1. Overall response rate (ORR = CR + PR) [ Time Frame: From randomization through study completion, on average within 9 months ]
    Defined as best confirmed response according to RECIST through study completion from randomization to either confirmed progression (by RECIST) or death from any cause

  2. Overall survival (OS) [ Time Frame: From randomization to death from any cause, on average within 18 months ]
    Defined as the duration from randomization to death from any cause or last follow-up.

  3. Disease control rate, DCR (=CR + PR + SD) [ Time Frame: From randomization through study completion, on average within 9 months ]
    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

  4. Number of patients with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: From the date the informed consent is signed up to 30 days after the last dose ]
    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.

  5. Quality of Life (QoL) assessed by QLQ-C30 [ Time Frame: From the date the informed consent is signed up to 30 days after the last dose ]
    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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • 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.

    •≥ 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.

Exclusion Criteria

  • 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02665039


Locations
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Denmark
Department of Oncology, Rigshospitalet
Copenhagen, Denmark, DK-2100
Sweden
Department of Oncology, Karolinska University Hospital
Stockholm, Sweden
Sponsors and Collaborators
Dr Anders Ullén
Investigators
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Principal Investigator: Anders Ullén, M.D., Ph.D. Karolinska University Hospital

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Responsible Party: Dr Anders Ullén, MD, PhD, Karolinska University Hospital
ClinicalTrials.gov Identifier: NCT02665039     History of Changes
Other Study ID Numbers: NUCOG I
First Posted: January 27, 2016    Key Record Dates
Last Update Posted: March 8, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Carcinoma
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Renal Insufficiency
Ureteral Neoplasms
Pelvic Neoplasms
Urethral Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Kidney Diseases
Ureteral Diseases
Urethral Diseases
Gemcitabine
Carboplatin
Vinblastine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors