Phase I study of nab-paclitaxel, gemcitabine, and bevacizumab in patients with advanced cancers

Br J Cancer. 2018 May;118(11):1419-1424. doi: 10.1038/s41416-018-0068-z. Epub 2018 Apr 26.

Abstract

Background: We performed a phase I modified 3 + 3 dose escalation study to evaluate the safety and activity of bevacizumab plus gemcitabine and nab-paclitaxel in patients with advanced solid tumours.

Methods: Patients were given fixed dose gemcitabine plus increasing doses of nab-paclitaxel and bevacizumab. Toxicity, response, and association with VEGF polymorphism was analysed.

Results: The study enrolled 110 patients who had undergone a median of 3 prior lines of therapy. The median age was 60 years (range, 17-85 years), and 55 patients (50%) had gemcitabine-refractory disease. We observed 3 dose-limiting toxicities during dose escalation and 3 DLTs in expansion cohorts. Dose escalation to 150 mg/m2 nab-paclitaxel and 15 mg/kg bevacizumab with 1000 mg/m2 of gemcitabine was well tolerated with no MTD. One patient with gemcitabine-refractory peritoneal papillary carcinoma had a complete response, 13 patients (13%) had partial responses, and 54 patients (52%) had stable disease ≥12 weeks. Exploratory VEGF single nucleotide polymorphism (SNP) analysis was performed on 13 patients.

Conclusions: The combination of gemcitabine, nab-paclitaxel, and bevacizumab is safe, well-tolerated, and has activity in advanced malignancies, including gemcitabine-refractory tumours. Based on this study, the recommended phase 2 dose is gemcitabine 1000 mg/m2, nab-paclitaxel 125 mg/m2, and bevacizumab 15 mg/kg. VEGF polymorphism data should be evaluated in future bevacizumab-based trials.

Trial registration: ClinicalTrials.gov NCT01113476.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Albumins / administration & dosage*
  • Albumins / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bevacizumab / administration & dosage*
  • Bevacizumab / adverse effects
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Drug Administration Schedule
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Paclitaxel / administration & dosage*
  • Paclitaxel / adverse effects
  • Polymorphism, Genetic
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / genetics
  • Young Adult

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Deoxycytidine
  • Bevacizumab
  • Paclitaxel
  • Gemcitabine

Associated data

  • ClinicalTrials.gov/NCT01113476