Phase I study of weekly treatment with paclitaxel injection concentrate for nanodispersion (PICN), a novel solvent and protein-free formulation of paclitaxel.

Abstract

3039 Background: PICN is a novel solvent and protein-free 100-110 nm particle formulation of paclitaxel stabilized with polymer and lipid using Nanotecton Technology. Paclitaxel has shown superior safety and efficacy profile when administered on a weekly schedule. We studied safety, tolerability, and pharmacokinetics (PK) of PICN using a weekly schedule in patients with advanced solid malignancies. Methods: Patients aged18-65 years with advanced solid malignancies, ECOG performance status ≤ 2, estimated survival ≥ 12 weeks, and adequate organ function were enrolled. A standard phase I, 3+3 dose escalation design to determine the maximum tolerated dose (MTD) of PICN administered on a weekly schedule (three consecutive weeks, one week recovery) was employed. PICN dose was escalated at pre-determined fixed dose levels of 80, 100, 125, 150, 175, and 200 mg/m2. PICN was administered as a 30 min infusion without any premedication for hypersensitivity. Results: Twenty-one patients treated with PICN had a mean age of 52.1 yrs (range 35-67); 20 were female and entered with metastatic breast cancer (MBC; n=15), cervical cancer (n=3), skin cancer (n=2). One male had oral cancer. Doses studied were 80 (n=3), 100 (n=3), 125 (n=3), 150 (n=3), 175 (n=6), and 200 (n=3) mg/m2. Despite the lack of dexamethasone premedication, no patient receiving PICN reported hypersensitivity reaction. Two DLTs (neutropenia and febrile neutropenia; both grade 3) were reported at PICN 200 mg/m2. PICN PK (AUC0-24, AUC0-∞, and Cmax) increased in a dose proportionate manner from 80 to 200 mg/m2. Grade 3 or worse related AEs were: neutropenia, leucopenia, peripheral neuropathy, febrile neutropenia, anemia, thrombocytopenia, fatigue, syncope, hypotension and maculopapular rash. Partial responses were observed in MBC (100, 125, 150, 175, and 200 mg/m2) and cervical cancer (80 mg/m2). Conclusions: PICN on thrice monthly schedule was tolerable in the dose range evaluated. Two DTLs were reported: neutropenia and febrile neutropenia (both grade 3). Anti-tumor activity was observed in MBC and cervical cancer. Final trial data for PICN PK, safety, and efficacy will be presented at the conference. Clinical trial information: CTRI/2011/11/002124.