Phase I Trial of Tandem Chemotherapy Cycles as Consolidation Therapy for High-Risk Epithelial Ovarian and Primary Peritoneal Cancer Utilizing Intraperitoneal Paclitaxel/IV Cyclophosphamide Followed by IV Topotecan/Intraperitoneal Cisplatin/IV Melphalan Using Hematopoietic Stem Cell Support
N/A
60 Years
Female
Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer
Trial Information
Phase I Trial of Tandem Chemotherapy Cycles as Consolidation Therapy for High-Risk Epithelial Ovarian and Primary Peritoneal Cancer Utilizing Intraperitoneal Paclitaxel/IV Cyclophosphamide Followed by IV Topotecan/Intraperitoneal Cisplatin/IV Melphalan Using Hematopoietic Stem Cell Support
OBJECTIVES:
- To establish the maximum tolerated dose (MTD) of continuous infusion intravenous
topotecan hydrochloride when administered with intraperitoneal (IP) cisplatin and
intravenous melphalan in patients with stage III, stage IV, or recurrent ovarian
epithelial cancer, primary peritoneal cancer, or fallopian tube cancer.
- To describe the toxicities of each dose studied.
- To evaluate the pharmacokinetics of topotecan hydrochloride when administered at the
maximum tolerated dose and cisplatin.
- To confirm the pharmacokinetic advantage of high-dose IP cisplatin and IP paclitaxel.
- To obtain tissue at the time of peritoneal catheter placement in order to evaluate the
molecular determinants of apoptosis (including p53 status, p21 gene expression, bcl-2
gene expression, and bcl-2/bax ratio) and the extent of apoptosis by the TdT assay.
- To evaluate the molecular determinants of DNA damage and repair, including expression
levels of ERCC1 and MDR1, and HER2/neu expression by immunohistochemistry.
OUTLINE: This is a dose-escalation study of topotecan hydrochloride.
Patients undergo surgical placement of an intraperitoneal (IP) catheter. Tumor biopsies are
obtained during surgery for laboratory analysis of molecular determinants of apoptosis
(including p53 status, p21 gene expression, bcl-2 gene expression, bcl-2/bax ratio) and
molecular determinants of DNA damage and repair (including expression levels of ERCC1 and
MDR1, and HER2/neu expression by immunohistochemistry). The extent of apoptosis is also
assessed using the TdT assay.
- Course 1: Patients receive paclitaxel IP on day 1, cyclophosphamide IV on day 2, and
filgrastim (G-CSF) subcutaneously (SC) beginning on day 3 and continuing until
apheresis is completed. Patients undergo apheresis until ≥ 2.5 X 10^6 CD34-positive
cells/kg are collected. Two weeks later, patients proceed to course 2.
- Course 2: Patients receive cisplatin IP and melphalan IV on days -11 and -4 and
topotecan hydrochloride by continuous infusion over 120 hours on days -10 to -6.
Patients receive 25% of their peripheral blood stem cells (PBSCs) on day -3 and G-CSF
IV beginning on day -3 and continuing until blood counts recover. Patients receive
their remaining PBSCs on day 0.
Patients undergo daily blood sample collection during topotecan hydrochloride administration
for pharmacokinetic studies. Patients treated at the maximum tolerated dose of topotecan
hydrochloride undergo additional blood sample collections for pharmacokinetic studies.
After completion of study therapy, patients are followed every 3 months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed ovarian epithelial carcinoma, primary peritoneal cavity
carcinoma, or epithelial carcinoma of the fallopian tubes, meeting 1 of the following
criteria:
- Stage III or IV disease that was treated with initial therapy comprising a
standard platinum-containing regimen
- Must have < 2 cm of residual disease with no evidence of disease
progression after initial chemotherapy AND have no disease progression
immediately prior to stem cell collection
- Patients initially presenting with stage IV disease who have achieved a
clinical response (complete response [CR] or partial response [PR]) after
initial therapy are eligible
- Responding recurrent disease
- Patients who have had recurrence with elevated CA 125 levels (> 100 U/mL)
and who have achieved a reduction of CA 125 level by 50% for 4 weeks
following the most recent course of reinduction chemotherapy are eligible
- Patients who have achieved a CR or PR after salvage chemotherapy for
relapsed disease are eligible
- Patients with measurable or evaluable disease must have achieved a PR after prior
therapy
- No clinically significant pleural effusions
PATIENT CHARACTERISTICS:
- Karnofsky performance status 70-100%
- ANC > 1,000/μL
- Platelet count > 100,000/μL
- Serum bilirubin < 1.5 mg/dL
- SGOT and SGPT ≤ 2.5 times normal
- Creatinine clearance ≥ 60 mL/min
- No active cardiac disease that, in the opinion of the investigator, would preclude
safe administration of chemotherapy
- Cardiac ejection fraction normal at rest by MUGA
- No history of potentially disabling psychiatric disorders
- Hepatitis B antigen, hepatitis C antibody, and HIV antibody negative
- No clinically significant peripheral neuropathy
- FEV_1 ≥ 2.0 L or ≥ 75% of the lower limit of normal
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 4 weeks since prior chemotherapy or radiotherapy
- No prior radiotherapy to the whole abdomen
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Primary Purpose: Treatment
Outcome Measure:
Toxicity
Safety Issue:
Yes
Principal Investigator
Robert J. Morgan, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Beckman Research Institute
Authority:
United States: Federal Government
Study ID:
00067
NCT ID:
NCT00550784
Start Date:
January 2001
Completion Date:
Related Keywords:
- Fallopian Tube Cancer
- Ovarian Cancer
- Peritoneal Cavity Cancer
- recurrent ovarian epithelial cancer
- stage III ovarian epithelial cancer
- stage IV ovarian epithelial cancer
- fallopian tube cancer
- peritoneal cavity cancer
- Ovarian Neoplasms
- Peritoneal Neoplasms
- Fallopian Tube Neoplasms
- Neoplasms, Glandular and Epithelial
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