MAJA: Clinical Trial With Vinflunine as Maintenance Therapy in Metastatic Urothelial Cancer

Sponsor

Spanish Oncology Genito-Urinary Group (Other)

Overall Status

Completed

CT.gov ID

NCT01529411

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

4.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a clinical trial to evaluate the efficacy and safety of the drug vinflunine administered after the standard treatment of the combination gemcitabine+cisplatin, when it has reached stabilization or response of the disease, as the first treatment inmeditely after the diagnosis of advanced or metastatic urothelial cancer.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Transitional Cell	Drug: Vinflunine Other: Undefined (standard care)	Phase 2

Detailed Description

Vinflunine is a drug recently approved in Europe for the treatment of advanced or metastatic urothelial cancer after platinum-failure. It has proved to improve the survival results compared with the best suportive care. In adition, the tolerability was favourable, specially for not leading appearance of neuropathy nor other cumulative toxic effects.

In this study, it is proposed to test the feasibility, in terms of tolerability and efficacy of monotherapy with vinflunine in patients who, after completing the first-line cisplatin-based treatment for Transitional Cell Carcinoma of the Urothelial Tract (CCTU), have reached a stabilization or objective response. In order to have an adequate control group in the proposed design will be a phase II trial in which one group will receive standard management (follow-up until progression disease).

Study Design

Study Type:

Interventional

Actual Enrollment :

86 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomized Phase II Study of Vinflunine as Maintenance Monotherapy in Patients With Advanced or Metastatic Urothelial Cancer That Obtains Clinical Benefit of the First Line With Cisplatin-gemcitabine Combination

Study Start Date :

Feb 1, 2012

Actual Primary Completion Date :

Feb 1, 2013

Actual Study Completion Date :

Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vinflunine Vinflunine 320 mg/m2 IV infusion in 20 minutes every 21 days (280mg/m2 if PS=1, age ≥ 75 years, previous pelvic radiotherapy or creatinine clearance < 60ml/min) + best suportive care, with regards clinical practice.	Drug: Vinflunine Vinflunine 320 mg/m2 IV infusion in 20 minutes every 21 days (280mg/m2 if PS=1, age ≥ 75 years, previous pelvic radiotherapy or creatinine clearance < 60ml/min). Other Names: Javlor
Other: Best suportive care Best suportive care	Other: Undefined (standard care) All the current interventions used by each institution for the study disease. Other Names: undefined

Arm

Intervention/Treatment

Experimental: Vinflunine

Vinflunine 320 mg/m2 IV infusion in 20 minutes every 21 days (280mg/m2 if PS=1, age ≥ 75 years, previous pelvic radiotherapy or creatinine clearance < 60ml/min) + best suportive care, with regards clinical practice.

Drug: Vinflunine

Vinflunine 320 mg/m2 IV infusion in 20 minutes every 21 days (280mg/m2 if PS=1, age ≥ 75 years, previous pelvic radiotherapy or creatinine clearance < 60ml/min).

Other Names:

Javlor

Other: Best suportive care

Best suportive care

Other: Undefined (standard care)

All the current interventions used by each institution for the study disease.

Other Names:

undefined

Outcome Measures

Primary Outcome Measures

Progression Free Survival. [1 year]
To evaluate the Progression Free Survival (PFS) with vinflunine in maintenance monotherapy in patients with advanced or metastatic CCTU that has reached stabilization or objective response after completing 6 cycles with the combination cisplatin-gemcitabine in 1st line.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age > 18 & < 80
Written informed consent given by the patient
Diagnosis of urothelium cells transition cancer subsidiary locally advanced or metastatic resection
One measurable target lesion minimum
ECOG 0 or 1
Stabilization or objective response after first-line treatment 6 cycles of cisplatin+gemcitabine
Last administration of cisplatin and gemcitabine < 6 weeks
Maximum grade I toxicity
Adequate functions of bone marrow, kidney and liver
Absence psychological, family, sociological or geographical disorder or other condition
Women of childbearing potential must be using a medically accepted method of contraception (i.e. oral contraceptives, intrauterine devices) to avoid pregnancy during the 2 months preceding the start of study treatment, throughout the study period and for up to 3 months after the last dose of study treatment in such a manner that the risk of pregnancy is minimised. Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the start of study treatment.
Fertile men must be using an effective method of birth control if their partners are women of childbearing potential up to 3 months after last administration of study medication.

Exclusion Criteria:

ECOG > 2
Patients with age > 80
Patients with small cell carcinoma histology, lymphomas or sarcomas of the bladder.
The patients that have received 7 or more cycles of a combination of cisplatin and gemcitabine in first line metastatic disease.
Pregnant or lactating women or women with positive pregnancy test at screening, fertile sexual active women that did not use or do not wish or are unable to use an accepted method to prevent pregnancy during the 2 months prior to study treatment, during the study period and up to 3 months after the last dose of study treatment. Sexual active men who do not wish to use a method of birth during the study and up to 6 months after the last dose of study treatment if their partners are women of childbearing age.
Known brain metastases or meningeal involvement. CT Scan not required to rule this unless there is clinical suspicion of disease of the central nervous system.
Peripheral neuropathy grade 2 according to NCI-CTC version 4.0 [Common Toxicity Criteria of the National Cancer Institute].
Prior radiation to > 30% of the bone marrow, radiation completed at least 30 days or current persistence of any adverse event.
Other serious diseases or medical conditions like: systemic infection that required a systemic anti-infective treatment(grades 3 or 4 of the Common Toxicity Criteria NCI, version 4.03) and uncontrolled medical disorder, for example: patients with unstable angina or myocardial infarction within 6 months before registration or uncontrolled diabetes.
Progressive Disease during 1st line treatment of advanced or metastatic disease with chemotherapy systemic cisplatin and gemcitabine.
Patients who have received more than one line of treatment for metastatic disease.
Patients who received cisplatin in monotherapy or in combination as neoadjuvant treatment, adjuvant after initial surgery of urothelial cancer.
Patients treated with another investigational drug or treatment antineoplastic agent cisplatin or gemcitabine than within 30 days before randomization.
Other cancers except basal skin cancer treated in an appropriate, cervical cancer in situ or other tumor a disease-free interval of 5 years.
Inadequate renal function defined by a calculated clearance serum creatinine < 40 ml/min (Cockcroft-Gault).
Known hypersensitivity to drug study or similar chemical structure drugs.
Patients who require treatment with ketoconazole, itraconazole, ritonavir, amprenavir, indinavir, rifampin or phenytoin (any potent inhibitor or inducer of CYP3A4).
Any concurrent chronic immunotherapy or prior organic allograft.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital General de Elda Virgen de la Salud	Elda	Alicante	Spain	03600
2	ICO-Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
3	ICO-Hospital Duran i Reynals	L'Hospitalet de Llobregat	Barcelona	Spain	08908
4	Hospital Fundació Althaia	Manresa	Barcelona	Spain	08243
5	Corporació Sanitaria Parc Taulí	Sabadell	Barcelona	Spain	08208
6	Complejo Hosp. Univ. de Santiago de Compostela	Santiago de Compostela	Galicia	Spain	15706
7	Hospital Universitario Fundación Alcorcón	Alcorcon	Madrid	Spain	28922
8	H. del Mar (Fundació Institut Mar d´Investigacions Mèdiques - FIMIM)	Barcelona		Spain	08003
9	H. Universitari Vall d'Hebrón	Barcelona		Spain	08035
10	Hospital Clínic i Provincial de Barcelona	Barcelona		Spain	08036
11	H. General Universitario de Ciudad Real	Ciudad Real		Spain	13005
12	Hospital General Universitario Gregorio Marañon	Madrid		Spain	28007
13	Hospital Clínico San Carlos	Madrid		Spain	28040
14	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
15	Hospital Universitari Son Espases	Palma de Mallorca		Spain	07010
16	Clínica Universitaria de Navarra (CUN)	Pamplona		Spain	31002
17	Complejo Hospitalario de Navarra	Pamplona		Spain	31008
18	H. Universitario Virgen de la Macarena	Sevilla		Spain	41009
19	H. Universitario Virgen del Rocío	Sevilla		Spain	41013
20	IVO	Valencia		Spain	46009

Sponsors and Collaborators

Spanish Oncology Genito-Urinary Group

Investigators

Principal Investigator: Jesús García-Donas, MD, Hospital Universitario Fundación Alcorcón
Principal Investigator: Albert Font, MD, ICO-Hospital Universitari Germans Trias i Pujol
Principal Investigator: Joaquim Bellmunt, MD, H. del Mar - FIMIM (Fundació Institut Mar d´Investigacions Mèdiques)