Evaluation of the safety of C-1311 (SYMADEX) administered in a phase 1 dose escalation trial as a weekly infusion for 3 consecutive weeks in patients with advanced solid tumours.
OBJECTIVE
C-1311 is a member of the novel imidazoacridinone family of anticancer agents. This phase 1 trial was designed to investigate the safety, tolerability and preliminary anti-tumour activity of C-1311.


METHODS
This was a phase 1, inter-subject dose escalating and pharmacokinetic study of intravenous (IV) C-1311, administered weekly during 3consecutive weeks followed by 1week rest (constituting 1 cycle) in subjects with advanced solid tumours.


RESULTS
Twenty-two (22) patients were treated with C-1311, the highest dose given was 640mg/m(2). All subjects experienced one or more treatment-related adverse events (AEs). The most frequently observed treatment-related AEs were neutropaenia and nausea (50% each), followed by vomiting (27%), anaemia (23%), asthenia (23%) and diarrhoea (18%). Most treatment-related AEs were of Common Terminology Criteria for Adverse Events (CTCAE) grades 1-2, except for the blood and lymphatic system disorders, which were primarily of grades 3-4. The recommended dose (RD) of C-1311 administered as once weekly IV infusions for 3weeks every 4weeks is 480mg/m(2), with the dose limiting toxicity (DLT) being grade 4 neutropaenia lasting more than 7days. Treatment at this dose offers a predictable safety profile and excellent tolerability.


CONCLUSIONS
The safety profile and preliminary anti-tumour efficacy of C-1311, observed in this broad-phase dose-finding study, warrants further evaluation of the compound.
Isambert
N
N
Department of Medical Oncology, Centre Georges-François Leclerc, 1 rue du Pr Marion, 21079 Dijon, France. nisambert@dijon.fnclcc.fr
Campone
M
M
Bourbouloux
E
E
Drouin
M
M
Major
A
A
Yin
W
W
Loadman
P
P
Capizzi
R
R
Grieshaber
C
C
Fumoleau
P
P
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000609:Aminoacridines / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D001682:Biological Availability; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D016896:Treatment Outcome
D000609:Aminoacridines; D000970:Antineoplastic Agents; C098965:C 1311