Trial of Vinflunine Versus Alkylating Agent in Metastatic Breast Cancer

NCT ID: NCT01091168

Last Updated: 2019-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 594 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2014-01-31

Brief Summary

In metastatic breast cancer (MBC) patients who have already received anthracyclines, taxanes, antimetabolites and vinca-alkaloids and have developed drug resistance to these drugs, therapeutic options are very limited. Alkylating agents showed a modest activity in pretreated metastatic breast cancer. This phase III trial will compare the effectiveness and the safety profile of vinflunine to an alkylating agent of physician choice in MBC patients who have exhausted anthracyclines, taxanes, antimetabolites and vinca-alkaloids.

Detailed Description

Breast cancer is the most frequently diagnosed cancer in women worldwide and the second leading cause of cancer-related deaths in women.

Patients with metastatic breast cancer (MBC) remains incurable, and current goals of therapy are to ameliorate symptoms, delay disease progression, improve or at least maintain quality of life (QoL), and prolong overall survival (OS).There are a number of agents with established single-agent activity, with the anthracyclines and taxanes considered generally the most active. In addition, several drugs with different mechanisms of action such as antimetabolites and vinca-alkaloids have also demonstrated substantial activity in the metastatic setting as single-agents or in combination.

In patients who progress after having received anthracyclines, taxanes, antimetabolites and vinca- alkaloids, therapeutic options are scarce. In this heavily pretreated population for whom overall survival is not expected to exceed 6 to 7 months, there is a clear need for novel therapies.

Vinflunine (VFL) is a microtubule inhibitor obtained by semi-synthesis, interacts with tubulin at the vinca-binding domain and inhibits tubulin assembly by perturbing microtubule dynamics and mitotic spindles without affecting assembled microtubules. VFL antitumour activity was fully demonstrated against a large and varied panel of murine and xenograft models.

The main haematological toxicity reported was the neutropenia Grade 3-4 (40-50%). The incidence of its complications (febrile neutropenia and neutropenic infection) was less than 8%. The main non-haematological toxicity Grade 3-4 (with an incidence more than 10%) reported were constipation and fatigue.

This was a prospective multicentre, open-label, randomised (1:1), phase III study comparing OS in patients treated with vinflunine versus those treated with an alkylating agent of physician's choice as third line treatment or more for patients with locally recurrent and/or metastatic breast cancer previously treated with and no longer candidate to anthracyclines, antimetabolites, taxanes and vinca- alkaloids..

The primary endpoint for the trial was OS. Patients were assessed for toxicity, tumour response and progression and status (alive-dead) at regular intervals during the study treatment and the follow-up period. Patients were treated until disease progression, unacceptable toxicity, patient or investigator's decision. After the study treatment discontinuation, patients were followed until death.

The VFL dose of 280 mg/m² was the selected dose for this phase III study in patients with heavily pre- treated MBC. Indeed, VFL dose was reduced from 320 to 280 mg/m² in advanced transitional cell carcinoma of urothelial tract patients with performance status (PS) of 1 or with PS of 0 and having received prior pelvic irradiation. This dose was more regularly tolerable in patients with advanced disease stage who were heavily pre-treated.

Conditions

Breast Cancer; Metastases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

arm A: Vinflunine

Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks.

Group Type: EXPERIMENTAL

vinflunine

Intervention Type: DRUG

280 mg/m2 on day 1 of each cycle every 3 weeks

arm B: Alkylating agent of physician choice

Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country.

Group Type: ACTIVE_COMPARATOR

Alkylating agent of physician choice registered in cancer

Intervention Type: DRUG

cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin

Interventions

vinflunine

280 mg/m2 on day 1 of each cycle every 3 weeks

Intervention Type: DRUG

Alkylating agent of physician choice registered in cancer

cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin

Intervention Type: DRUG

Other Intervention Names

JAVLOR; L00070; Various

Eligibility Criteria

Inclusion Criteria

• Female patients 18 to 75 years of age with metastatic breast cancer histologically/cytologically confirmed not amenable to curative surgery or radiotherapy and who have received at least two prior chemotherapy regimens including anthracyclines,taxanes,antimetabolite and vinca-alkaloid and are no longer candidate for these drugs,
• Karnofsky performance score of at least 70 %, adequate haematological, hepatic and renal functions and ECG without clinically relevant abnormality.

Exclusion Criteria

• Concurrent serious uncontrolled medical disorder,
• known or clinical evidence of brain metastases or leptomeningeal involvement,
• pulmonary lymphangitis or symptomatic pleural effusion or symptomatic ascites,
• history of second primary malignancy,
• HIV infection, preexisting neuropathy,
• pregnancy or breast feeding.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Pierre Fabre Medicament

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karim Keddad, MD, PhD

Role: STUDY_DIRECTOR

Institut de Recherche Pierre Fabre

Locations

Buenos Aires, , Argentina

Quilmes, , Argentina

Rosario, , Argentina

San Martín, , Argentina

San Miguel de Tucumán, , Argentina

Graz, , Austria

Salzburg, , Austria

Vienna, , Austria

Grodno, , Belarus

Homyel, , Belarus

Minsk, , Belarus

Vitebsk, , Belarus

Brussels, , Belgium

Haine-Saint-Paul, , Belgium

Yvoir, , Belgium

Angers, , France

Brest, , France

Clermont-Ferrand, , France

Dijon, , France

Grenoble, , France

Le Mans, , France

Lille, , France

Limoges, , France

Lorient, , France

Montpellier, , France

Nancy, , France

Nantes, , France

Nice, , France

Paris, , France

Pontoise, , France

Reims, , France

Rouen, , France

Saint-Brieuc, , France

Saint-Priest-en-Jarez, , France

Strasbourg, , France

Berlin, , Germany

Dortmund, , Germany

Essen, , Germany

Mainz, , Germany

Munich, , Germany

Trier, , Germany

Ancona, , Italy

Aviano, , Italy

Bolzano, , Italy

Brindisi, , Italy

Frattamaggiore, , Italy

Macerata, , Italy

Orbassano, , Italy

Lisbon, , Portugal

Arkhangelsk, , Russia

Engel's, , Russia

Moscow, , Russia

Ryazan, , Russia

Saint Petersburg, , Russia

Saratov, , Russia

Stavropol, , Russia

Tambov, , Russia

Ufa, , Russia

Volgograd, , Russia

Durban, , South Africa

Johannesburg, , South Africa

Pretoria, , South Africa

A Coruña, , Spain

Barcelona, , Spain

Madrid, , Spain

Seville, , Spain

Taichung, , Taiwan

Taipei, , Taiwan

Taoyuan District, , Taiwan

Dnipropetrovsk, , Ukraine

Kharkiv, , Ukraine

Khmelnytskyi, , Ukraine

Kyiv, , Ukraine

Burnley, , United Kingdom

Cornwell, , United Kingdom

Derby, , United Kingdom

Glasgow, , United Kingdom

Ipswich, , United Kingdom

Preston, , United Kingdom

Worthing, , United Kingdom

Countries

Argentina; Austria; Belarus; Belgium; France; Germany; Italy; Portugal; Russia; South Africa; Spain; Taiwan; Ukraine; United Kingdom

References

Cortes J, Perez-Garcia J, Levy C, Gomez Pardo P, Bourgeois H, Spazzapan S, Martinez-Janez N, Chao TC, Espie M, Nabholtz JM, Gonzalez Farre X, Beliakouski V, Roman Garcia J, Holgado E, Campone M. Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer. Ann Oncol. 2018 Apr 1;29(4):881-887. doi: 10.1093/annonc/mdy051.

Reference Type: DERIVED

PMID: 29481630 (View on PubMed)

Other Identifiers

L00070 IN 308 B0

Identifier Type: -

Identifier Source: org_study_id