Pazopanib with low fat meal (PALM) in advanced renal cell carcinoma

Invest New Drugs. 2019 Apr;37(2):323-330. doi: 10.1007/s10637-018-0692-8. Epub 2018 Nov 5.

Abstract

Background Pazopanib is approved for metastatic renal cell carcinoma (RCC). We assessed the safety and efficacy of pazopanib with a low fat meal (LFM): <400 cal and < 20% fat or 10 g per meal. Methods A single arm study of pazopanib with a LFM in 16 adult patients with metastatic RCC with a clear cell component, RECIST 1.1 measurable disease, ECOG PS ≤ 2, and ≤ 3 prior therapies. Pazopanib at 400 mg daily given with LFM for 12 weeks. Incremental dose increases up to 800 mg, or irreversible decreases to 200 mg, allowed every 2 weeks. Primary study endpoint was safety; adverse events (AE) measured per CTCAE version 4.0. Secondary endpoints of RECIST 1.1 response with assessment as 12 weeks; pharmacokinetic (PK) analysis at nine time points, and CYP3A4 polymorphism evaluation. Results Pazopanib with a LFM was well tolerated; 13 of 16 subjects completed all 12 weeks. Three patients withdrew due to adverse events (AEs), with five occurrences of grade 3 AEs. Conclusions Pazopanib with a LFM has acceptable safety and comparable efficacy to fasting administration. Total median pazopanib dose per subject for the study duration was 63.5% of maximum possible conventional dose. A larger study is warranted. Clinical Trial Registration Number: NCT02729194.

Keywords: Advanced disease; Fat meal; Pazopanib; Renal cell carcinoma; Tyrosine kinase inhibitor therapy.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / therapy*
  • Combined Modality Therapy
  • Diet, Fat-Restricted / methods*
  • Female
  • Follow-Up Studies
  • Humans
  • Indazoles
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / therapy*
  • Male
  • Middle Aged
  • Prognosis
  • Pyrimidines / therapeutic use*
  • Sulfonamides / therapeutic use*

Substances

  • Angiogenesis Inhibitors
  • Indazoles
  • Pyrimidines
  • Sulfonamides
  • pazopanib

Associated data

  • ClinicalTrials.gov/NCT02729194