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

NCT ID: NCT02665039

Last Updated: 2019-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2018-09-30

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.

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.

Conditions

Urothelial Carcinoma; Bladder Cancer; Renal Pelvis Cancer; Ureter Cancer; Urethra Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Vinflunine

Intervention Type: DRUG

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

Intervention Type: DRUG

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

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

Group Type: ACTIVE_COMPARATOR

Gemcitabine

Intervention Type: DRUG

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

Carboplatin

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Carboplatin

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

Intervention Type: DRUG

Other Intervention Names

Javlor®; Gemzar; Karboplatin

Eligibility 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.

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dr Anders Ullén

OTHER

Sponsor Role: lead

Responsible Party

Dr Anders Ullén

MD, PhD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Anders Ullén, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Karolinska University Hospital

Locations

Department of Oncology, Rigshospitalet

Copenhagen, , Denmark

Department of Oncology, Karolinska University Hospital

Stockholm, , Sweden

Countries

Denmark; Sweden

References

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.

Reference Type: DERIVED

PMID: 31648851 (View on PubMed)

Other Identifiers

NUCOG I

Identifier Type: -

Identifier Source: org_study_id