Open Trial of Bendamustine Hydrochloride in Women With Advanced Ovarian Cancer

Bendamustine, a non-cross resistant cytotoxic, has potential to offer a new regimen for the
treatment of ovarian cancer in women who are refractory to standard drug regimens. Non-cross
resistance to platinum is critical for the development of effective salvage regimens in this
platinum resistant population. In addition bendamustine's cytotoxic effects are thought to
occur via several mechanistic pathways, apoptosis, DNA repair, DNA replication, DNA
transcription. The study seeks to determine the efficacy and safety of bendamustine in women
with advanced ovarian cancer.

Inclusion Criteria:

1. Patients must have histologically or pathologically confirmed diagnosis of epithelial
carcinoma of the ovary, fallopian tube cancer or primary peritoneal serous papillary
carcinoma. Borderline ovarian tumors are not allowed.

2 Patients must have relapsed within 6 months of completing, or had a best response of
increasing disease during any number of prior chemotherapy regimens with a platinum (either
cisplatin or carboplatin) and a taxane (paclitaxel or docetaxel). These agents may have
been administered concurrently or sequentially. Any number of additional regimens for
recurrent disease will be allowed, as long as the patient performance status is 0-2
Gynecologic Oncology Group (GOG).

3 Patients must have measurable or evaluable (i.e. positive serum Cancer Antigen (CA) -125
marker) disease. Scans or physical examinations used for tumor measurement must have been
completed within 28 days prior to registration. Scans or ultrasounds for non -measurable
disease must have been performed within 28 days prior to registration.

4 Prior radiation is allowed as long as it encompassed no more than 25% of the bone marrow.
Debulking surgery for relapsed disease is allowed as long as the patient has measurable or
evaluable disease remaining after the surgery. Patient must have recovered from all side
effects of surgery.

5 Patients must not have received chemotherapy, biologic therapy or any other
investigational drug for any reason within 28 days prior to registration. Patients must not
have had a major surgery within 14 days prior to registration.

6 Patients must have a GOG performance status of 0-2.

7 Patients must have adequate liver function as defined by a serum bilirubin ≤2.0 x the
institutional upper limit of normal (IULN), serum glutamic-oxaloacetic transaminase (SGOT)
or serum glutamic-pyruvic transaminase (SGPT) ≤2.5 x the institutional upper limit of
normal obtained within 14 days prior to registration.

8 Patients must have an adequate renal function as defined by a serum creatinine ≤1.5x the
institutional upper limit of normal obtained within 14 days prior to registration

9 Patients must not have Class 3 /4 cardiac problems as defined by the New York Heart
Association Criteria (e.g., congestive heart failure, myocardial infarction within 2 months
of study)

10 Patients must not be pregnant or nursing as bendamustine maybe harmful to the developing
fetus and newborn. Women of reproductive potential must have a negative serum pregnancy
test within 7 days prior to registration. Post-menopausal women must be amenorrheic for at
least 12 months to be considered of non-childbearing potential. Patients of reproductive
potential must agree to employ an effective barrier method of birth control throughout the
study and for up to 3 months following discontinuation of study drug.

11 No other prior malignancy is allowed except for the following: adequately treated basal
cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or
II cancer from which the patient is currently in complete remission, or any other cancer
from which the patient has been disease-free for 5 years.

12 Patients must have the following hematological criteria: Hemoglobin of ≥9gm/dL White
blood cell count ≥ 2500 Platelets ≥ 100,000

13 Patients must be ≥ 18 years of age.

Exclusion Criteria:

1. No borderline ovarian tumors and mixed mesodermal soft tissue sarcomas

2. No psychological, familial, sociological, or geographical conditions that do not
permit medical follow-up or compliance with the study protocol

3. Except for cancer-related abnormalities, patients should not have unstable or
preexisting major medical conditions

4. No medical life-threatening complications of their malignancies

5. No known severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled
diabetes, uncontrolled chronic renal or liver disease, active uncontrolled infection,
or HIV)

6. Inadequately controlled hypertension (defined as systolic blood pressure ≥ 150 and/or
diastolic blood pressure ≥100 mmHg on antihypertensive medications)

7. New York Heart Association (NYHA) Grade III or greater congestive heart failure

8. Evidence of 5 to ≤10% loss of weight from baseline (baseline defined as the screening
weight taken approximately 14 days of Day 0) that is not related to ascites or
paracentesis.

9. Evidence of uncontrollable nausea

10. Presence of central nervous system or brain metastases

11. Known hypersensitivity to any component of bendamustine HCL