A Pilot Study of Low-Dose Interleukin-2 Plus Recombinant Human Anti-HER2 Monoclonal Antibody in Solid Tumors

Trial Information

A Pilot Study of Low-Dose Interleukin-2 Plus Recombinant Human Anti-HER2 Monoclonal Antibody in Solid Tumors

OBJECTIVES: I. Determine the toxic effects of humanized anti-HER2 monoclonal antibodies when
administered in combination with interleukin-2 (IL-2) in patients with solid tumors. II.
Measure in vitro cytotoxicity using peripheral blood mononuclear cells, plasma, and target
cell lines that express HER2 in this patient population. III. Phenotypically characterize
effector cells at the time of antibody administration and 24 hours after three days of
intermediate dose IL-2 pulsing in these patients. IV. Measure antitumor response in these
patients.

OUTLINE: Cohorts of 6 patients are enrolled at 4 antibody dose levels. After at least 6
patients have been treated on study for at least 30 days, the next dose level may be
initiated provided that fewer than 2 of the first 6 evaluable patients experience dose
limiting toxicity (DLT) related to either the antibody or the combination of antibody with
interleukin-2 (IL-2). If 2 or more patients experience DLT, the next cohort is enrolled at
the antibody dose midway between the current and previous dose levels. An additional 6
patients are entered at the maximum tolerated dose. On course 1, patients receive IL-2
subcutaneously (SQ) daily on days 1-7 and humanized anti-HER-2 monoclonal antibodies IV over
90 minutes on day 7. Patients receive intermediate dose pulsed IL-2 SQ on days 8-10 and low
dose IL-2 SQ on days 11-20. On course 2 and all subsequent courses, patients receive
humanized anti-HER2 monoclonal antibodies IV immediately prior to IL-2 (SQ) on day 1 and
intermediate dose pulsed IL-2 (SQ) on days 1-3. Patients receive low dose IL-2 (SQ) on days
4-14. Treatment may be delayed up to 7 days to allow for recovery and for tumor restaging,
but daily low dose IL-2 is continued in this interval. Patients are followed at 4 weeks and
then every 8 weeks until progression or death.

PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study.