Combination Chemotherapy With CS-1008 to Treat Ovarian Cancer

• objective response rate (all subjects) [ Time Frame: 18 weeks = 6 cycles ] [ Designated as safety issue: No ]
• duration of complete response [ Time Frame: 18 weeks = 6 cycles ] [ Designated as safety issue: No ]
• overall survival (subjects that achieve a complete response) [ Time Frame: 18 weeks = 6 cycles ] [ Designated as safety issue: No ]

This is a trial to see what effects a combination therapy with CS-1008 and Paclitaxel/Carboplatin will have on a patient's response in locally advanced or metastatic ovarian cancer.

• Drug: CS-1008
  CS-1008 IV infusion up to 10 mg/kg once every 3 weeks (1 cycle) for 6 cycles
• Drug: paclitaxel
  paclitaxel 175 mg/m2 IV infusion once every 3 weeks (1 cycle) for 6 cycles
  Other Name: Taxol
• Drug: carboplatin
  carboplatin (target area under the concentration versus time curve of 6.0 using the Calvert Formula) IV infusion once every 3 weeks (1 cycle) for 6 cycles

Inclusion Criteria:

• Histologically confirmed, epithelial carcinoma of the ovary or primary peritoneal carcinoma (FIGO Stage IIIC or IV). (Subjects with the following histologic epithelial cell types are eligible for the study: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified.)
• Enrollment within 6 weeks after surgical resection (debulking).
• Residual tumor masses > 1 cm and objectively measurable/evaluable disease as defined by RECIST criteria.
• No prior therapy for ovarian cancer (ie, chemotherapy or radiotherapy [RT] to the abdomen or pelvis) other than surgical debulking of disease.
• At least 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

• Adequate organ and bone marrow function as evidenced by:

  • Absolute neutrophil count ≥ 1,500/µL (equivalent to NCI CTCAE, Version 3.0 grade 1)
  • Platelet count ≥ 100,000/µL (CTCAE grade 0 to 1)
  • Hemoglobin ≥ 9 g/dL
  • Serum creatinine ≤ 1.5 x institutional ULN (CTCAE grade 1)
  • Bilirubin ≤ 1.5 x ULN (CTCAE grade 1)
  • AST and alkaline phosphatase ≤ 2.5 x ULN (CTCAE grade 1)
• Adequate neurologic function (ie, sensory and motor neuropathy ≤ CTCAE grade 1).
• Women of childbearing potential must be willing to consent to using effective contraception while on treatment and for 3 months thereafter.
• All subjects of childbearing potential must have a negative pregnancy test (serum or urine) result ≤ 72 hours before initiating study treatment.
• Subjects must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an IRB-approved ICF before performance of any study-specific procedures or tests.

Exclusion Criteria:

• Prior invasive malignant disease within 5 years except for squamous cell or basal cell carcinoma.
• Current diagnosis of borderline epithelial ovarian tumor (formerly "tumors of low malignant potential") or recurrent ovarian epithelial cancer.
• Positive human immunodeficiency virus (HIV) or hepatitis B surface antigen (HBsAg) because of the potential for additional toxicity from the treatment regimen.
• Anticipation of need for a major surgical procedure or RT during the study.
• History of any of the following conditions within 6 months before study enrollment: myocardial infarction; severe/unstable angina pectoris; coronary/peripheral artery bypass graft; New York Heart Association (NYHA) class III or IV congestive heart failure; cerebrovascular accident or transient ischemic attack, pulmonary embolism, or other clinically significant thromboembolic event; clinically significant pulmonary disease (eg, severe chronic obstructive pulmonary disease or asthma).
• Clinically active brain metastasis (ie, untreated, still requiring therapy with steroids or RT, or with progression within 4 weeks after completion of RT); an uncontrolled seizure disorder; spinal cord compression; or carcinomatous meningitis.
• Pregnant or lactating.
• Prior treatment with CS-1008, other agonistic DR5 antibodies, or TRAIL.
• Known history of hypersensitivity reactions to any of the components of CS-1008, paclitaxel (or docetaxel), or carboplatin formulations.
• Serious intercurrent medical or psychiatric illnesses or any other conditions that in the opinion of the Investigator would impair the ability to give informed consent or unacceptably reduce protocol compliance or safety of the study treatment.