Combination Chemotherapy With CS-1008 to Treat Ovarian Cancer
Condition: Ovarian Cancer Stage IIIC; Ovarian Cancer Stage IV
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: CS-1008; Paclitaxel; Carboplatin
Intervention description: CS-1008 intravenous (IV) infusion 10 mg/kg on Day 1 of Cycle 1 and 8 mg/kg once every 3 weeks (1 cycle) for Cycle 2-6; Paclitaxel 175 mg/m^2 IV infusion once every 3 weeks (1 cycle) for 6 cycles; Carboplatin (target area under the concentration versus time curve of 6.0 mg/mL/min using the Calvert Formula) IV infusion once every 3 weeks (1 cycle) for 6 cycles
Intervention MeSH terms: Paclitaxel; Carboplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ovarian Cancer Stage IIIC; Ovarian Cancer Stage IV; CS-1008; Paclitaxel; Carboplatin

Summary:

      This trial assessed the effect of treatment with CS-1008 in combination with
      paclitaxel/carboplatin on response in patients with locally advanced or metastatic ovarian
      cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed, epithelial carcinoma of the ovary or primary peritoneal
             carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stage IIIC or
             IV).

        (Participants 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 Response Evaluation Criteria in Solid Tumors (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 National Cancer Institute
                  (NCI) Common Terminology Criteria for Adverse Events (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 upper limit of normal (ULN) (CTCAE grade
                  1)

               -  Bilirubin ≤ 1.5 x ULN (CTCAE grade 1)

               -  Aspartate aminotransferase (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.

          -  Participants 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 institutional review board-approved informed consent form (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 radiotherapy (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 tumor necrosis
             factor-related apoptosis inducing ligand (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.