Combination Chemotherapy and Autologous Peripheral Stem Cell Transplant in Treating Patients With Stage III, Stage IV, or Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer
Primary Purpose
Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
filgrastim
cisplatin
cyclophosphamide
melphalan
paclitaxel
topotecan hydrochloride
TdT-mediated dUTP nick end labeling assay
gene expression analysis
immunohistochemistry staining method
pharmacological study
peripheral blood stem cell transplantation
Sponsored by
About this trial
This is an interventional treatment trial for Fallopian Tube Cancer focused on measuring recurrent ovarian epithelial cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, fallopian tube cancer, peritoneal cavity cancer
Eligibility 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
Sites / Locations
Outcomes
Primary Outcome Measures
Toxicity
Tumor response
Reason patient is removed from study
Disease progression
Overall survival
Progression-free survival
Time to progression
Secondary Outcome Measures
Full Information
NCT ID
NCT00550784
First Posted
October 22, 2007
Last Updated
October 3, 2014
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00550784
Brief Title
Combination Chemotherapy and Autologous Peripheral Stem Cell Transplant in Treating Patients With Stage III, Stage IV, or Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
January 2001 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
5. Study Description
Brief Summary
RATIONALE: Giving chemotherapy before a peripheral stem cell transplant stops the growth of tumor cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.
PURPOSE: This phase I trial is studying the side effects and best dose of topotecan when given together with cyclophosphamide, paclitaxel, melphalan, and cisplatin, followed by an autologous peripheral stem cell transplant in treating patients with stage III, stage IV, or recurrent ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer
Keywords
recurrent ovarian epithelial cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, fallopian tube cancer, peritoneal cavity cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Allocation
Non-Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Intervention Type
Drug
Intervention Name(s)
topotecan hydrochloride
Intervention Type
Genetic
Intervention Name(s)
TdT-mediated dUTP nick end labeling assay
Intervention Type
Genetic
Intervention Name(s)
gene expression analysis
Intervention Type
Other
Intervention Name(s)
immunohistochemistry staining method
Intervention Type
Other
Intervention Name(s)
pharmacological study
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Primary Outcome Measure Information:
Title
Toxicity
Title
Tumor response
Title
Reason patient is removed from study
Title
Disease progression
Title
Overall survival
Title
Progression-free survival
Title
Time to progression
10. Eligibility
Sex
Female
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert J. Morgan, MD
Organizational Affiliation
City of Hope Comprehensive Cancer Center
Official's Role
Study Chair
12. IPD Sharing Statement
Learn more about this trial
Combination Chemotherapy and Autologous Peripheral Stem Cell Transplant in Treating Patients With Stage III, Stage IV, or Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer
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