PHASE I STUDY OF INTERFERON ENHANCED INTRAPERITONEAL RADIOIMMUNO-CHEMOTHERAPY FOR OVARIAN CANCER
18 Years
N/A
Female
Ovarian Cancer, Primary Peritoneal Cavity Cancer
Trial Information
PHASE I STUDY OF INTERFERON ENHANCED INTRAPERITONEAL RADIOIMMUNO-CHEMOTHERAPY FOR OVARIAN CANCER
OBJECTIVES:
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
patients.
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
177Lu-CC49.
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
(90Y-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
year.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma of the ovary or papillary serous carcinoma of
extraovarian origin
- Recurrent or persistent following standard surgery and 1 or 2 chemotherapy regimens
(with or without paclitaxel), i.e.: persistent disease or progression after
chemotherapy with nodules less than the equivalent of 5 x 5 x 5 cm Recurrent
carcinoma (after primary or secondary chemotherapy) detected clinically either by
exam or rising CA 125 and with radiographic evidence of disease no greater than the
equivalent of 5 x 5 x 5 cm nodules
- Residual disease less than 5 x 5 x 5 cm following reassessment laparotomy
- Microscopic residual disease on reassessment laparotomy after chemotherapy
- Tumor TAG-72 positive by immunoperoxidase staining of original or current tumor
blocks
- At least 85% free flow of fluid in peritoneal cavity demonstrated by technetium-99m
scan or other imaging within 2 weeks prior to treatment
- No evidence of disease outside the peritoneal cavity other than retroperitoneal
lymphadenopathy
- No massive ascites
PATIENT CHARACTERISTICS:
- Age: 18 and over
- Performance status: ECOG 0-2
- WBC at least 3,500/mm3
- Platelet count at least 125,000/mm3
- Hemoglobin greater than 9 g/dL
- No nucleated RBC or significant teardrop RBC morphology
- Bilirubin less than 1.5 mg/dL
- AST/ALT less than 4 times normal
- Creatinine less than 2.0 mg/dL
- HIV negative
- Hepatitis B surface antigen negative
- No hypersensitivity to paclitaxel, polyoxethylated castor oil, or topotecan
- No other malignancy in past 5 years except basal cell skin carcinoma
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- At least 3 weeks since prior biologic therapy and recovered
- No prior monoclonal antibody therapy
- No concurrent immunotherapy
- No prior bone marrow or stem cell transplantation
- At least 3 weeks since prior chemotherapy (6 weeks since nitrosoureas or mitomycin)
and recovered
- No concurrent chemotherapy
- At least 3 weeks since prior radiotherapy and recovered
- No prior radiotherapy to the abdominal cavity
- No concurrent radiotherapy
- At least 3 weeks since prior major surgery and recovered
- No prior intraperitoneal therapy
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Ruby F. Meredith, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
University of Alabama at Birmingham
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02240
NCT ID:
NCT00002734
Start Date:
March 1996
Completion Date:
Related Keywords:
- Ovarian Cancer
- Primary Peritoneal Cavity Cancer
- recurrent ovarian epithelial cancer
- primary peritoneal cavity cancer
- Ovarian Neoplasms
- Peritoneal Neoplasms
Name | Location |
|---|---|
| University of Alabama Comprehensive Cancer Center | Birmingham, Alabama 35294 |
