Phase Ib/II Study Assessing the Neo-adjuvant Combination Therapy of Vinflunine With Cisplatin Followed by Radical Cystectomy in Patients With Muscle-invasive Bladder Cancer (JaNEO)

NCT02845050 | Withdrawn Phase 1 DMC

• 2 other identifiers: JaNEO-0012016-000081-33
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Phase Ib/II study assessing the neo-adjuvant combination therapy of vinflunine with cisplatin followed by radical cystectomy in patients with muscle-invasive bladder cancer (JaNEO).

Conditions

Bladder Cancer

Keywords

neo-adjuvant; vinflunine; cisplatin; radical cystectomy; muscle-invasive bladder cancer; JaNEO

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR)

  Rate of pathological complete response (pCR) at cystectomy assessed by central pathological review (Prof. Hartmann, Erlangen), if the initial safety phase allows continuation of the trial with the phase II part

  cystectomy

Secondary Outcomes (8)

• Overall radiological response rate before cystectomy

  prior cystectomy

• Progression rate

  after 2 and 4 cycles (of 21 days length) of treatment

• Safety of chemotherapy measured by adverse events and clavien-dindo grades

  through study completion after 12 months-follow up

• Rate of complications at cystectomy

  at cystectomy

• Perioperative morbidity/mortality

  30 days and 90 days post surgery

Other Outcomes (2)

• Relapse rate and location of relapse not RECIST-standardized

  at 1 month, 3 months and 1 year after cystectomy

• Biobanking

  Day 1 of cyle 1-4, Day 15 of cyle 1, at cystectomy, 1, 3 and 12 months follow up, and baseline for tumour tissue

Study Arms (1)

Vinflunine+Cisplatin+radical cystectomy

EXPERIMENTAL

neoadjuvant combination of Vinflunine+Cisplatin before radical cystectomy as proof of principle (one arm only!)

Drug: Vinflunine; Drug: Cisplatin; Procedure: Radical cystectomy

Interventions

Vinflunine DRUG

One cycle is defined as a period of 3 weeks of treatment: Vinflunine (280 mg/m²) on Day 1, every 21 days as a 20 minute IV infusion Cisplatin (70 mg/m²) on Day 2, every 21 days 4 cycles of neo-adjuvant chemotherapy prior to radical cystectomy

Vinflunine+Cisplatin+radical cystectomy

Cisplatin DRUG

One cycle is defined as a period of 3 weeks of treatment: Vinflunine (280 mg/m²) on Day 1, every 21 days as a 20 minute IV infusion Cisplatin (70 mg/m²) on Day 2, every 21 days 4 cycles of neo-adjuvant chemotherapy prior to radical cystectomy

Vinflunine+Cisplatin+radical cystectomy

Radical cystectomy PROCEDURE

max. 4 weeks after 4 cycles of neo-adjuvant treatment radical cystectomy will be performed

Vinflunine+Cisplatin+radical cystectomy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged ≥ 18 years and ≤ 75 years with legal capacity
• Signed written informed consent
• Histologically confirmed muscle-invasive urothelial cell carcinoma of the bladder (MIBC) with clinical T2-T4a (N0/Nx, M0) assessed by primary PDD-guided TUR-B and by the screening imaging (MRI pelvis and CT chest/abdomen) which both must include the use of contrast medium
• Confirmed adequate complete resection of all visible tumor during TUR-B according to current treatment guidelines before registration; the latest TUR-B must have been done ≤ 8 weeks before registration
• ECOG performance status of 0 or 1
• Adequate bone marrow, renal and hepatic functions as evidenced by the following:
• Absolute Neutrophil Count ≥ 2,000 mm3 and ≤ 7,500 mm3
• Hemoglobin ≥ 12 g/dL for the safety phase of the study; if the study treatment proved to be adequate tolerated during this safety phase, the threshold can be lowered to ≥ 10 g/dL according to the decision of the study steering committee
• Platelet count ≥ 100,000 mm3
• Serum albumin within normal range
• Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Transaminases (ALT, AST) ≤ 1.5 x ULN
• Creatinine clearance ≥ 60 mL/min, calculated based on a 24h-measured creatinine clearance
• Serum Urea \< 25 mg/100 ml
• Absence of psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; these conditions should be assessed with the patient before registration

You may not qualify if:

• Prior systemic chemotherapy for any kind of malignancy; prior intravesical chemotherapy or treatment with BCG is allowed
• Prior radiation of the pelvis or any prior radiation to ≥ 30 % of the bone marrow
• Evidence of lymph node (N+) or distant metastasis (M1) in the screening imaging assessment, including known brain metastases or leptomeningeal involvement (however, brain-MRI-scans are not required to rule out CNS-involvement, unless there is clinical suspicion of central nervous system (CNS) disease)
• Any contraindication with regard to contrasted imaging (MRI or CT)
• Other malignancies except adequately treated basal carcinoma of the skin, localized prostate cancer Gleason ≤ 6, in-situ cervix carcinoma or any other tumor with a disease free interval ≥ 5 years
• Peripheral neuropathy Grade ≥ 2 NCI CTCAE v4.03 or hearing impairment Grade ≥ 2 NCI CTCAE v.4.03
• Any concurrent chronic system immune therapy or previous organ allograft
• Weight loss \> 5 % within the last 3 months before registration
• Any other serious illness or medical condition including:
• Infection requiring systemic anti-infective therapy within the last 2 weeks before registration
• History of cardio-vascular disease that might compromise the safe administration of cisplatin
• Dehydration requiring IV fluid substitution
• Any medical condition that might not be controlled, e.g. patients with unstable angina pectoris, myocardial infarction \< 6 months before registration or uncontrolled diabetes, congestive cardiac failure \> NYHA grade I
• Known hypersensitivity to the study drugs or to drugs with similar chemical structures
• Treatment with any potent CYP3A4 inhibitor or inductor (e.g. ketoconazole, itraconazole, ritonavir, amprenavir, indinavir, rifampicine) or phenytoine; replacement of such treatment with alternative treatment options before start of study treatment is acceptable, if medically feasible and ethically acceptable

Sponsors & Collaborators

• Ligartis GmbH: lead

Study Sites (2)

Dept. Urology, University Hospital Marburg

Marburg/ Lahn, Baldingerstraße, 35033, Germany

Location

Dept. Urology, University Hospital Tübingen

Tübingen, Hoppe-Seyler-Straße 3, 72076, Germany

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

vinflunine; Cisplatin; Cystectomy

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2016
• First Posted: July 27, 2016
• Study Start: July 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: February 13, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)