Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 22, No 14S (July 15 Supplement), 2004: 2049
© 2004 American Society of Clinical Oncology

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Abstract

Phase I trial of a nucleoside analog CP-4055 given daily for 5 days every 3 weeks in patients (pts) with advanced solid tumors - preliminary results

Univeristy of South Alabama, Cancer Research Inst, Mobile, AL; Norwegain Radium Hospital, Oslo, Norway; Princess Royal Hospital, Hull, United Kingdom; University of Surrey, Guildford, United Kingdom; Church House, Hungerford, United Kingdom; Clavis Pharma AS, Oslo, Norway

2049

Background: CP-4055 is a novel optimized nucleoside analog with a wide spectrum of pre-clinical activity in solid tumors due to improved uptake, reduced efflux and resistance to deamination. We report on the first phase I trial in pts with advanced non-small-cell lung cancer (NSCLC), malignant melanoma (MM) and ovarian cancer (OC). Methods: CP-4055 is administered for 5 consecutive days (d) every 3 weeks in a 30-min infusion at 30, 60, 100, 150 and 175 mg/m²/d, 3 pts/dose level (DL) in the absence of dose limiting toxicity (DLT). Standard hematological, biological and clinical DLT definitions are used. Activity is assessed every 2 cycles (cy). PK is determined in all pts at d 1 and 4 of cy 1 Results: : From Dec 02 to Dec 03, 17 pretreated pts (NCSCL: 2 pts, MM: 10 pts, OC: 5 pts) received in total 45 cy of CP-4055 (median 2, range 1–8), M/F: 6 / 11. Three pts were treated at each DL, apart from 5 pts at DL5 (175 mg/m²) due to an apparent DLT. Accrual is ongoing. Safety: The main treatment-related adverse events (AEs) are nausea and vomiting, neutropenia, anemia and moderate fatigue. No significant unexpected AEs occurred, while non-DLT hematological grade 3 and 4 toxicities were seen at the 2 last DLs explored. Efficacy: Stable disease was noted in 6 out of 17 pts, all of whom had progressive disease at inclusion. One NSCLC pt (60 mg/m²) had stabilization of lung lesions for 10+ months in addition to complete resolution of pleural effusion. One OC pt (60 mg/m²) had a reduction of CA125 (189 to 83) in addition to stable disease (2.5 months). Four MM pts (30, 60 [2 pts] and 175 mg/m²) had disease stabilization between 7 and 17 weeks. PK data, linear between DL1 and 4, suggest an intracellular CP-4055 reservoir with sustained Ara-U release. Conclusions: The MTD is expected to be DL5 (175 mg/m²) or 6 (200 mg/m²). On the basis of the favorable safety profile and evidence of activity, further development including schedule/regimen optimization, combination studies and phase II activity exploration are planned.

Author Disclosure

Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Clavis Pharma AS Clavis Pharma AS

Abstract presentation from the 2004 ASCO Annual Meeting