Vinorelbine in Advanced BRAF-like Colon Cancer

Summary

Vecchione et al showed that suppression of RANBP2 results in mitotic defects only in BRAF-like colon cancer (CC) cells, which leads to cell death. Mechanistically, RANBP2 silencing reduces microtubule outgrowth from the kinetochores, thereby inducing spindle perturbations, providing an explanation for the observed mitotic defects. Vinorelbine mimics RANPB2 silencing in BRAF-like and BRAFV600E CC cell lines.

These preclinical data represent a strong rationale to also explore the anti-tumor activity of vinorelbine in patients with advanced BRAF-like (both BRAFm and BRAF wild type) CC. Tumors having this gene signature are referred to as "BRAF-like" and have a similar poor prognosis irrespective of the presence of BRAF(V600E) mutation. Since vinorelbine is standard of care in advanced breast and NSCLC, there is ample experience with the dose and schedule as well as with the safety profile and supportive measures required to prevent side-effects.

Conditions

• Colon Cancer

Interventions

DRUG

Vinorelbine Tartrate

Intravenous administration of vinorelbine on day 1 and day 8 in a dose of 30 mg/m2. One treatment cycle is 21 days.

Sponsors & Collaborators

• Vall d'Hebron Institute of Oncology

  collaborator OTHER

• Agendia

  collaborator INDUSTRY

• European Organisation for Research and Treatment of Cancer - EORTC

  collaborator NETWORK

• Azienda Ospedaliera Niguarda Cà Granda

  collaborator OTHER

• Fundación para la Investigación del Hospital Clínico de Valencia

  collaborator OTHER

• University of Campania Luigi Vanvitelli

  collaborator OTHER

• University of Turin, Italy

  collaborator OTHER

• Eli Lilly and Company

  collaborator INDUSTRY

• Catalan Institute of Health

  collaborator OTHER_GOV

• Universitaire Ziekenhuizen KU Leuven

  collaborator OTHER

• The Netherlands Cancer Institute

  lead OTHER

Principal Investigators

• N Steeghs, MD, PhD · NKI-AvL

• J Tabernero, Prof · VHIO

• R Salazar, MD, PhD · ICO

• R Bernards, Prof · Agendia

• S Siena, Prof · ONCG

• A Cervantes, Prof · Instituto de Investigacion Sanitaria INCLIVA

• F Ciardiello, Prof · Instituto de Investigacion Sanitaria INCLIVA

• A Bardelli, Prof · UNITO

• S Tejpar, Prof · UZ Leuven

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-03-01

Primary Completion

2020-03-17

Completion

2020-03-17

Countries

• Netherlands

Study Locations