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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02665039
• Date of registration: 18/01/2016
• Prospective Registration: No
• Primary sponsor: Dr Anders Ullén
• Public title: A Trial With Vinflunine in Patients With Metastatic Bladder Cancer and Impaired Renal Function VINGEM
• Scientific 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.
• Date of first enrolment: April 2014
• Target sample size: 62
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02665039
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Denmark, Sweden

Contacts

• Name: Anders Ullén, M.D., Ph.D.
• Affiliation: Karolinska University Hospital

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Bladder Cancer

Ureter Cancer

Urothelial Carcinoma

Renal Pelvis Cancer

Urethra Cancer

Intervention(s)

Drug: Carboplatin

Drug: Gemcitabine

Drug: Vinflunine

Primary Outcome(s)

Progression-free survival (PFS) [Time Frame: From randomization through study completion, on average within 9 months]

Secondary Outcome(s)

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]

Overall response rate (ORR = CR + PR) [Time Frame: From randomization through study completion, on average within 9 months]

Overall survival (OS) [Time Frame: From randomization to death from any cause, on average within 18 months]

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

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]

Secondary ID(s)

NUCOG I

Source(s) of Monetary Support

Please refer to primary and secondary sponsors