PHASE I STUDY OF INTERFERON ENHANCED INTRAPERITONEAL RADIOIMMUNO-CHEMOTHERAPY FOR OVARIAN CANCER
I. Determine the maximum tolerated dose (MTD) of intraperitoneal paclitaxel and topotecan
when administered as a radiosensitizer prior to intraperitoneal lutetium Lu 177 monoclonal
antibody CC49 (177Lu-CC49) following subcutaneous interferon alfa-2b (IFN-A) in patients
with persistent or recurrent ovarian cancer.
II. Determine the toxicity associated with intraperitoneal paclitaxel and topotecan in these
III. Examine the conjugate stability, pharmacokinetics, and biodistribution of 177Lu-CC49
given 48 hours after intraperitoneal paclitaxel.
IV. Determine the effects of IFN-A and intraperitoneal paclitaxel on 177Lu-CC49 tumor
localization and dosimetry estimates compared to a prior trial with 177Lu-CC49 alone.
V. Determine the MTD of yttrium Y 90 monoclonal antibody CC49 (90Y-CC49) when administered
with IFN-A and the dose of paclitaxel used at the MTD level of IFN-A, paclitaxel, and
VI. Monitor any antitumor effects of this treatment in these patients.
OUTLINE: This is a dose escalation study of paclitaxel, topotecan, lutetium LU 177
monoclonal antibody CC-49 (177Lu-CC49), and yttrium Y 90 monoclonal antibody CC49
Patients receive interferon alfa subcutaneously on days 1, 3, 5, and 7; paclitaxel
intraperitoneally (IP) on day 4 or topotecan IP on day 6; and 177Lu-CC49 IP on day 6.
Treatment continues every 6 weeks for 2 courses in the absence of disease progression or
unacceptable toxicity. Cohorts of 3-5 patients receive escalating doses of paclitaxel and
decreasing doses of 177Lu-CC49 until the maximum tolerated dose (MTD) is determined. The MTD
is defined as the dose preceding that at which 3 of 5 patients experience dose limiting
toxicity. Once the MTD of paclitaxel is determined, the dose of 177Lu-CC49 is escalated.
Once the MTD of 177Lu-CC49 is determined, 90Y-CC49 is substituted. The MTD of 90Y-CC49 is
then determined when administered with paclitaxel. Topotecan is then substituted for
paclitaxel (administered with the MTD of 177Lu-CC49 and interferon alfa only) and escalated
until the MTD is determined. Patients are followed at 6 weeks and then every 3 months for 1
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Ruby F. Meredith, MD, PhD
University of Alabama at Birmingham
United States: Food and Drug Administration
|University of Alabama Comprehensive Cancer Center||Birmingham, Alabama 35294|