Brief Title
A Trial With Vinflunine in Patients With Metastatic Bladder Cancer and Impaired Renal Function
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.
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Progression-free survival (PFS)
Secondary Outcome
Overall response rate (ORR = CR + PR)
Condition
Urothelial Carcinoma
Intervention
Vinflunine
Study Arms / Comparison Groups
Vinflunine + gemcitabine
Description: 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
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
62
Start Date
April 2014
Completion Date
September 2018
Primary Completion Date
September 2018
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.
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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Anders Ullén, M.D., Ph.D., ,
Location Countries
Denmark
Location Countries
Denmark
Administrative Informations
NCT ID
NCT02665039
Organization ID
NUCOG I
Responsible Party
Sponsor-Investigator
Study Sponsor
Dr Anders Ullén
Study Sponsor
Anders Ullén, M.D., Ph.D., Principal Investigator, Karolinska University Hospital
Verification Date
October 2019