Alimta® Plus Cisplatin & Paclitaxel Given Intraperitonelly; First Line Tx Stage III Ovarian Cancer
Condition: Fallopian Tube Cancer; Ovarian Cancer; Peritoneal Cavity Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms
Intervention: cisplatin; paclitaxel; pemetrexed disodium; biologic sample preservation procedure
Intervention description: IP cisplatin will be administered on day 2 of each cycle at 75mg per m2 and IP paclitaxel will be administered at 60mg per m2 on day 8 of each cycle. Courses will be repeated every 21 days for up to 6 cycles; IP cisplatin will be administered on day 2 of each cycle at 75mg per m2 and IP paclitaxel will be administered at 60mg per m2 on day 8 of each cycle. Courses will be repeated every 21 days for up to 6 cycles; Escalate doses in groups of 3 patients to 60mg per m2, 120 mg per m2, 500 mg per m2, 750 mg per m2, 1000 mg per m2; Plasma samples will be collected on the 1st course at baseline, 30 minutes, 60 minutes, 2 hours, 4 hours, 6 hours (if possible) and 24 hours after the first IP Alimta® dose.
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Cisplatin; Pemetrexed
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage III ovarian epithelial cancer; recurrent ovarian epithelial cancer; peritoneal cavity cancer; fallopian tube cancer

Summary:

      RATIONALE: Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth. Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in
      different ways to stop the growth of tumor cells, either by killing the cells or by stopping
      them from dividing. Giving pemetrexed together with cisplatin and paclitaxel and giving them
      in different ways may kill more tumor cells.

      PURPOSE: This phase I trial is studying the side effects and best dose of intraperitoneal
      pemetrexed when given together with intraperitoneal cisplatin and paclitaxel in treating
      patients with stage III ovarian epithelial cancer, primary peritoneal cancer, or fallopian
      tube cancer.
    

Eligibility 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 Central nervous system (CNS) or brain metastases

        PATIENT CHARACTERISTICS:

          -  Gynecologic Oncology Group performance status 0-2

          -  White blood cell count(WBC) ≥ 3,500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Hemoglobin ≥ 9 g/dL

          -  Serum bilirubin ≤ 2 times upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST)and alanine aminotransferase (ALT) ≤ 2.5 times upper
             limit of normal

          -  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