Phase I Open Label Trial of Alimta® Plus Cisplatin and Paclitaxel Given Intraperitoneally (IP) as First Line Treatment for Women With Stage III Ovarian Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or pathologically confirmed ovarian epithelial carcinoma, primary
peritoneal carcinoma, or fallopian tube carcinoma

- Stage III disease

- Meets 1 of the following criteria:

- No prior treatment and no more than 6 months since primary surgery

- Platinum-sensitive at second-look surgery with no prior cisplatin therapy

- Must have been optimally debulked to less than 2-cm residual individual tumor plaques
or, if suboptimally debulked at first surgery, had chemical debulking

- No mixed Müllerian tumor or borderline ovarian tumor

- No CNS or brain metastases

PATIENT CHARACTERISTICS:

- GOG performance status 0-2

- WBC ≥ 3,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9 g/dL

- Serum bilirubin ≤ 2 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN

- Creatinine clearance ≥ 45 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception during and for 3 months
after discontinuation of study drug

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

- No unstable or preexisting major medical conditions, except cancer-related
abnormalities

- No medical life-threatening complications of their malignancies

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

- No serious active uncontrolled infections

- No inadequately controlled hypertension (defined as systolic blood pressure ≥ 150 mm
Hg and/or diastolic blood pressure ≥ 100 mm Hg on antihypertensive medications)

- No New York Heart Association grade II-IV congestive heart failure

- No weight loss between 5 to ≤ 10% within the past 14 days that is not related to
ascites or paracentesis

- No prior hypertensive crisis or hypertensive encephalopathy

- No myocardial infarction, cerebrovascular accident, transient ischemic attack, or
unstable angina within the past 6 months

- No evidence of uncontrollable nausea

- No clinically significant or symptomatic peripheral vascular disease (e.g., aortic
aneurysm or aortic dissection)

- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess

- No pre-existing clinically significant hearing loss

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer, cervical carcinoma in situ, or adequately treated stage I
or II cancer from which the patient is in complete remission

- No known hypersensitivity to any component of pemetrexed disodium

- Able to take folic acid, vitamin B_12, and dexamethasone according to protocol

- No presence of third-space fluid that cannot be controlled by drainage

- No inability to comply with study and/or follow-up procedures

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- May have received up to 4 courses of carboplatin and paclitaxel IV as neoadjuvant
chemotherapy for advanced, unresectable disease

- Concurrent low-dose aspirin therapy (i.e., 325 mg/day) allowed

- Concurrent ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) with
short elimination half-lives allowed provided ≥ 1 of the following criteria is met:

- Creatinine clearance (CrCl) > 80 mL/min (i.e., normal renal function)

- CrCl 45-79 mL/min (i.e., mild to moderate renal insufficiency) AND NSAID dosing
interrupted for a period of 2 days before, during, and 2 days after
administration of pemetrexed disodium

- Concurrent NSAIDs or salicylates with long half-lives (e.g., naproxen, piroxicam,
diflunisal, or nabumetone) allowed provided NSAID dosing is interrupted for at least
5 days before, during, and 2 days after administration of pemetrexed disodium

- No concurrent antineoplastic or antitumor agents not part of the study therapy (i.e.,
chemotherapy, radiotherapy, immunotherapy, or hormonal anticancer therapy)

- No other concurrent investigational agents