477P - Phase I trial of intraperitoneal nab-paclitaxel in the treatment of advanced malignancies primarily confined to the peritoneal cavity

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Presenter Mihaela Cristea
Citation Annals of Oncology (2014) 25 (suppl_4): iv146-iv164. 10.1093/annonc/mdu331
Authors M.C. Cristea1, S. Rivkin2, D. Lim1, V. Chung1, J. Chao1, M. Wakabayashi1, B. Paz1, E. Han1, P. Lin1, L. Leong1, A. Hakim1, P. Frankel1, T. Synold1, M. Carroll1, H. Openshaw1, N. Prakash1, T. Dellinger1, M. Park2, R. Morgan1
  • 1Medical Oncology, City of Hope, 91010 - Duarte/US
  • 2Oncology, Swedish Cancer Institute, Seattle/US

Abstract

Aim

The primary objective was to determine maximum tolerated dose (MTD) and the potential PK advantage of IP nab-paclitaxel (favorable peritoneal cavity ratio of nab-paclitaxel: plasma).

Methods

Phase I study of IP nab-paclitaxel, D1, 8, 15; 28-day cycle; 3 + 3 dose-escalation design in patients (pts) with advanced ovarian cancer primarily confined to the peritoneal cavity, unresponsive to previous regimens, or for which no standard regimens exist. Pts had pre-study IP catheters placed, and had plasma and peritoneal pharmacokinetic (PK) studies on C1D1 and C1D15

Results

25 pts were enrolled; 2 were inevaluable as they did not complete cycle 1 due to port failure, and leucopenia not qualifying as dose limiting toxicity (DLT). Cohort 1 (35mg/m2), 2 (70mg/m2), and 3 (90mg/m2) were completed without DLT. 6 pts were accrued to Cohort 4 (112mg/m2); one had DLT (leukopenia resulting in treatment delay >15 days). Cohort 5 (140mg/m2) at first enrolled 3 pts with no DLT. Cohort 6 (170mg/m2) enrolled 3 pts; one had DLT (grade 3 abdominal pain and grade 4 neutropenia) and one had grade 4 neutropenia and treatment-related asymptomatic drop in the ejection fraction, neither qualifying as DLT. We concluded that dose level 6 was too toxic; no further Cohort 6 pts were enrolled. We expanded Cohort 5 to 5pts with no DLT (MTD). PK data show a ∼150-fold pharmacologic advantage to IP nab-paclitaxel with low inter- and intra-pt variability. Plasma AUCs from IP nab-paclitaxel are ∼50% of plasma AUCs from IV delivery of the same dose; thus patients are exposed to therapeutic systemic drug levels.

Conclusions

The MTD of IP nab-paclitaxel is 140 mg/m2. PK data reveal a significant peritoneal advantage, and the tolerable toxicity suggests that nab-paclitaxel is ideal for IP delivery. Further studies of combination therapy are indicated. Study approval/funding - NCCN; Research support - Celgene Corp

Disclosure

B. Paz: Speakers Bureau – Genomic Health, Inc. Stock Shareholder – LS Biopath. All other authors have declared no conflicts of interest.