This pilot study will help us to determine the success of using a special technique called
microarray technology to examine cancer genes in order to predict how individual women will
respond to one of two therapies, liposomal doxorubicin or topotecan, and which will be more
effective in treating ovarian cancer that has returned (recurrent ovarian cancer). We believe
that this study may lead to a means by which microarray technology can predict the most
effective treatment decision, based on the genetic characteristics of her tumor tissue, for a
woman with recurrent ovarian cancer.
Another purpose of this study is to determine how quickly a woman with recurrent ovarian
cancer will respond to treatment (treatment response rate) and to evaluate the accuracy of
the genomic predictions.
Recent data suggest that microarray technology can predict a patient's response to
chemotherapy; this has not yet been proven in a forward-looking study which is why we are
conducting this research.
Patients who take part in the study will have an initial visit and undergo a CT guided core
biopsy. Using tissue from a CT guided core biopsy, microarray analysis will be performed to
help predict which of the two drugs appears to be better suited to individual genomic
factors. The results will result in being assigned to treatment with either liposomal
doxorubicin or topotecan.
Patients who receive liposomal doxorubicin - IV chemotherapeutic treatment will occur 3
times, 28 days apart, weeks 1,5,and 9. At each of these visits patients will be evaluated and
have blood work to check their liver tests and electrolytes. Every 8 weeks patients will have
a radiologic evaluation of their tumor.
Patients who receive topotecan - IV chemotherapeutic treatment will occur 4 times, 21 days
apart, weeks 1,4,7, and 10. At each of these visits patients will be evaluated and have blood
work to check levels of liver tests and electrolytes. Every 8 weeks patients will have a
radiologic evaluation of their tumor.
- Must have history of histologically or cytologically confirmed epithelial ovarian
cancer with recurrence.
- Must have measurable disease, defined as at least one lesion that can be accurately
measured in at least one dimension (longest diameter to be recorded) as >20 mm with
conventional techniques or as >10 mm with spiral computed tomography CT) scan.
- May have had only 2 prior chemotherapy regimens, with at least one regimen containing
platinum, and disease recurrence or progression occurring between 0 to 12 months (1 to
365 days)from the platinum-containing regimen. Patients who have been treated with
consolidation treatment are allowed and the consolidation will not be considered a
separate regimen. Hormonal therapy and immunotherapy will not be considered a prior
chemotherapy regimen. Hormonal therapies given to treat the patient's cancer should be
stopped at least 30 days prior to dosing on this trial. Typical low-dose hormone
replacement therapy to treat postmenopausal symptoms may be continued at the treating
- Life expectancy >6 months.
- ECOG performance status 2 or less (Karnofsky 60%).
- Must have normal organ and marrow function as defined below:
- leukocytes 3,000/microL
- absolute neutrophil count 1,500/ microL
- platelets 100,000/microL
- total bilirubin ≤1.5 X institutional upper limit of normal(ULN) aspartate
aminotransferase [AST(SGOT)]/alanine aminotransferase [ALT(SGPT)] ≤2.5 X ULN
creatinine within normal institutional limits OR creatinine clearance
60mL/min/1.73m2 for patients with creatinine levels above institutional normal
- Ability to understand and willingness to sign a written informed consent document
- Measurable disease on CT must be considered amenable to biopsy by Core methods (core
biopsy may be radiographically or non-radiographically performed). Potential ability
to obtain core material must be reviewed by Principal Investigator (PI) and/or his
designates prior to enrollment.
- Must consent to biopsy as part of enrolling into trial.
- Patients with reproductive potential must use an adequate contraceptive method (e.g.
abstinence, intrauterine device, oral contraceptives, barrier device with spermicide
or surgical sterilization) during treatment and for three months after completing
- Must have a Multiple Gated Acquisition (MUGA) scan or 2-d echocardiogram indicating an
ejection fraction of > 50% or institutional standards within 42 days prior to first
dose of study drug. The method used at baseline must be used for later monitoring.
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not version
13, 01/10/08 MCC 15042 16 recovered from adverse events due to agents administered
more than 4 weeks earlier.
- May not be receiving any other investigational agents concurrently.
- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse events.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to liposomal doxorubicin or topotecan.
- Myocardial infarction within 6 months. History of cardiac disease, with New York Heart
Association Class II or greater, or clinical evidence of congestive heart failure.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
- Women who are pregnant.
- Women who are breastfeeding should discontinue breastfeeding.
- Human Immunodeficiency Virus (HIV)-positive patients receiving combination
anti-retroviral therapy are excluded from the study because of possible
pharmacokinetic interactions and increased toxicity.
- Patients may have had no other malignancies in the prior 5 years other than
non-metastatic, locally-controlled, non-melanomatous cutaneous cancers.
- Patients who have received radiation to more than 25% of marrow-bearing areas.