Pralatrexate is a type of antifolate drug which means is restrains the production of folic acid in the body. Folic acids are used by tumors to increase tumor cell growth and division. It is believed that reducing folic acid will hinder the rapid division of tumor cells, their growth and production. Carboplatin is an FDA approved chemotherapy drug for ovarian, fallopian tube and primary peritoneal cancer. Some antifolate drugs are used with other chemotherapy drugs to enhance cancer-fighting characteristics. It is believed that the study drug pralatrexate may improve the anti-tumor effect of carboplatin. In this research study we are looking for the highest dose of pralatrexate that can be given safely in combination with carboplatin.

• Since we are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects, not everyone who participates will receive the same dose of the study drug.
• Each study cycle will last 28 days. On Day 1, participants will receive carboplatin intravenously. On Days 1 and 15 of each cycle they will receive pralatrexate intravenously. Participants will also be asked to take folic acid orally on a daily basis starting 7 days before the first dose of pralatrexate and continuing until 30 days after the last dose of pralatrexate. They will also receive a vitamin B12 injection no more than 10 weeks prior to the first dose of pralatrexate and every 8-10 weeks after the first dose of pralatrexate.
• Participants will come to the clinic on Day 1 and 15 of each cycle and have the following tests/procedures performed: Medical history; Vital signs; Blood tests, assessment of the tumor (every two cycles) and an EKG (before the start of cycle 2).
• In addition, during Cycle 1, participants will come to the clinic weekly for blood tests.
• Pharmacokinetic (PK) blood samples (to monitor how the body absorbs and breaks down the study drug) will be done at the following time points during Cycle 1: Day 1-3 and Day 15-17.
• Participants will be asked to take the study drugs for up to 6 cycles. They may continue beyond 6 cycles as long as there is evidence that the tumor is not growing and they are not experiencing any unacceptable side effects.

Inclusion Criteria:

• Patients must be diagnosed with a platinum-sensitive recurrence of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
• The following histologic subtypes are eligible: papillary serous, endometrioid, mucinous, clear cell, adenocarcinomas, transitional, and mixtures of the above.
• Patients must have at least one measurable lesion according to RECIST criteria via CT or MRI scan. CT of the chest should be performed if any known disease is present in the chest. Pleural effusions, ascites, bone metastases, CA125 tumor markers, and lesions located in previously radiated areas are not considered measurable.
• Patients must have received a platinum-containing regimen at initial diagnosis.
• ECOG Performance Status of 0, 1 or 2
• Patients may have received up to 2 prior chemotherapy regimens in the recurrent cancer setting
• 18 years of age or older
• Life expectancy of greater than 12 weeks
• Baseline laboratory values must meet what is outlined in the protocol
• Patients must receive vitamin B12 and folic acid prior to starting treatment
• Complete recovery from previous chemotherapy or biologic therapy
• During the Phase II of the study, patients with significant ascites and/or pleural effusions will undergo consideration of drainage of these areas prior to starting carboplatin and pralatrexate.
• Women of childbearing potential must have a negative pregnancy test within 7 days prior to initiating chemotherapy on trial and must agree to practice effective method of birth control during the study and for six months after their last treatment.
• Patients must have a normal QTc interval

Exclusion Criteria:

• Prior pelvic radiotherapy to greater than 25% of bone marrow
• Any uncontrolled medical problem that in the opinion of the investigator would preclude safe administration of the study drugs.
• Past history of bone marrow transplantation or stem cell support
• Patient with known history of CNS metastasis is ineligible unless the patient has had treatment with surgery or radiation therapy, is neurologically stable, and does not require oral or intravenous corticosteroids or anticonvulsants.
• A history of prior malignancy except for adequately treated carcinoma in situ of the uterine cervix, incidental stage I endometrial cancer, basal cell or squamous cell skin cancer, or breast cancer (invasive or ductal carcinoma in situ) for which the patient has been disease-free for at least three years.
• Routine prophylactic use of G-CSF or GM-CSF within two weeks prior to study entry.
• Clinically significant cardiac disease
• Uncontrolled hypercalcemia or diabetes mellitus
• Any signs of intestinal obstruction that interfere with bowel function and/or nutrition
• Grade 2 or greater peripheral neuropathy
• Participation in an investigational study within three weeks prior to study entry.
• History of anaphylactic shock to prior platinum chemotherapy that would preclude safe administration of study carboplatin.
• History of psychiatric disability or other central nervous system disorder as judged by the principal investigator that would be considered significant and that would preclude informed consent, safe administration of study medications and affecting ability to comply with study procedures.
• Doses of ibuprofen in excess of 400mg QID.
• Interval cytoreductive surgery planned for while subject is on-study.
• Recurrence/progression within 6 months of receiving ay platinum regimen
• Patients with either pleural effusions or ascites are not eligible for Phase I of the study