Phase II trial of intravenous CI-1042 in patients with metastatic colorectal cancer.
OBJECTIVE
To evaluate the antitumor activity, safety, immune response, and replication of CI-1042 (ONYX-015), an E1B 55-kd gene-deleted replication-selective adenovirus, administered intravenously to patients with metastatic colorectal cancer


METHODS
Eighteen patients with metastatic colorectal cancer for whom prior chemotherapy failed were enrolled onto an open-label, multicenter, phase II study. CI-1042 was administered intravenously at a dose of 2 x 1012 viral particles every 2 weeks. Patients were evaluated for tumor response and toxicity; in addition, blood samples were taken for adenovirus DNA and neutralizing antibody analysis.


RESULTS
Common toxicities included flu-like symptoms, nausea, and emesis. All 18 patients eventually were removed from study because of progressive disease. Seven patients were assessed as having stable disease after 2 months of treatment, whereas two patients were considered to have stable disease after 4 months. Detectable circulating CI-1042 DNA was identified in 36% of patients 72 hours after last infusion, which is suggestive of ongoing viral replication.


CONCLUSIONS
In this phase II study, intravenous CI-1042 was administered safely to patients with advanced colorectal cancer. Toxicity was manageable, consisting primarily of flu-like symptoms. Stable disease was experienced by seven patients for 11 to 18 weeks.
Hamid
Oday
O
Pfizer Global Research and Development, 2800 Plymouth Rd, Ann Arbor, MI 48105, USA. oday.hamid@pfizer.com
Varterasian
Mary L
ML
Wadler
Scott
S
Hecht
J Randolph
JR
Benson
Al
A
Galanis
Evanthia
E
Uprichard
Margaret
M
Omer
Charles
C
Bycott
Paul
P
Hackman
Robert C
RC
Shields
Anthony F
AF
D000256:Adenoviridae / Q000276:immunology; D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000032:analysis; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001344:Autopsy; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014018:Tissue Distribution; D017211:Treatment Failure; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000956:Antigens, Viral; D000970:Antineoplastic Agents; D014765:Viral Vaccines; C464532:dl1520