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

NCT02665039 | Completed Phase 2 DMC

• 1 other identifier: NUCOG I
• Study Type: interventional
• Target: 62
• Locations: 2 countries
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

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

  From randomization through study completion, on average within 9 months

Secondary Outcomes (5)

• Overall response rate (ORR = CR + PR)

  From randomization through study completion, on average within 9 months

• Overall survival (OS)

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

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

  From randomization through study completion, on average within 9 months

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

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

• Quality of Life (QoL) assessed by QLQ-C30

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

Study Arms (2)

Vinflunine + gemcitabine

EXPERIMENTAL

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; Drug: Gemcitabine

Carboplatin + gemcitabine

ACTIVE COMPARATOR

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; Drug: Carboplatin

Interventions

Vinflunine 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

Also known as: Javlor®

Vinflunine + gemcitabine

Gemcitabine 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

Also known as: Gemzar

Carboplatin + gemcitabine; Vinflunine + gemcitabine

Carboplatin DRUG

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

Also known as: Karboplatin

Carboplatin + gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• Dr Anders Ullén: lead

Study Sites (2)

Department of Oncology, Rigshospitalet

Copenhagen, DK-2100, Denmark

Location

Department of Oncology, Karolinska University Hospital

Stockholm, Sweden

Location

Related Publications (1)

• 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.

  PMID: 31648851 DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Ureteral Neoplasms; Urethral Neoplasms

Interventions

vinflunine; Gemcitabine; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Ureteral Diseases; Urethral Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Study Officials

• Anders Ullén, M.D., Ph.D.

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: January 18, 2016
• First Posted: January 27, 2016
• Study Start: April 1, 2014
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: October 8, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1); SE (1)