DO/NDR/02 a novel polymeric nanoparticle paclitaxel: Results of a phase I dose escalation study

Abstract

2026 Background: DO/NDR/02 is a novel Cremophor free Paclitaxel formulation in which the drug is delivered as nano micelles using a polymeric carrier. A phase I dose escalation study evaluating a three weekly regimen is being conducted to determine the maximum tolerated dose (MTD), safety profile and pharmacokinetic (PK) profiles of this formulation when given to refractory or metastatic solid tumors. Method: DO/NDR/02 was administered as a one-hour infusion without premedications in doses ranging from 135 to 375 mg/m2 for a maximum of six cycles. Serial blood samples were collected for PK analysis during cycles 1 and 2 and Paclitaxel concentrations were determined using a validated HPLC method. Results: Twenty-three patients have been treated at various dose levels up to 375mg/m2. Till date there has been no incidence of hypersensitivity reactions, febrile neutropenia or neuropathies above grade 1. The major non-hematological toxicities were grade 3 infection without neutropenia (n=1) seen at 135 mg/m2 and grade 3 diarrhea (n = 2) at 300 and 375 mg/m2 respectively. The major hematological toxicities have been grade 4 neutropenia (n = 2) at 135 and 375 mg/m2. The MTD has been determined at 375mg/m2. Objective responses (OR) are seen in 6 out of 18 (33.3%) patients evaluated so far. 5 out of 10 (50%) cases of heavily pretreated breast cancer have shown OR. PK analysis has shown a linear correlation between the mean AUC and dose up to 375mg/m2. Conclusions: The initial results of this study reveals that DO/NDR/02 may be safely administered without any premedications, to a higher dose than Cremophor Paclitaxel. It has also shown a linear PK profile and encouraging clinical activity in advanced breast cancers. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Dabur Research Foundation Dabur Research Foundation Dabur Research Foundation Dabur Research Foundation