Phase I clinical trial of nintedanib plus paclitaxel in early HER-2-negative breast cancer (CNIO-BR-01-2010/GEICAM-2010-10 study)

Br J Cancer. 2014 Sep 9;111(6):1060-4. doi: 10.1038/bjc.2014.397. Epub 2014 Jul 24.

Abstract

Introduction: Previous small-molecule antiangiogenics have compromised chemotherapy dose intensity in breast cancer. We present a phase I trial of a novel selective agent, nintedanib, plus standard chemotherapy in early breast cancer.

Methods: Her-2-negative breast cancer patients with tumours larger than 2 cm were eligible for dose-escalation trial (classic 3+3 method).

Results: The recommended phase II dose (RP2D) was 150 mg BID of nintedanib combined with standard dose of weekly paclitaxel followed by adriamycin plus cyclophosphamide. The dose-limiting toxicity was transaminase elevation. At the RP2D, the dose intensity was ∼100%. The pathologic complete response was 50%.

Conclusions: The combination allows the delivery of full-dose intensity, while efficacy seems promising.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Aspartate Aminotransferases / blood
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Female
  • Humans
  • Indoles / administration & dosage
  • Indoles / adverse effects
  • Lymphopenia / chemically induced
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoadjuvant Therapy
  • Neutropenia / chemically induced
  • Paclitaxel / administration & dosage
  • Prospective Studies
  • Receptor, ErbB-2 / analysis
  • Treatment Outcome
  • gamma-Glutamyltransferase / blood

Substances

  • Indoles
  • Doxorubicin
  • Cyclophosphamide
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • nintedanib
  • Paclitaxel