Second-Line Therapy Study For Potentially Platinum-Sensitive Relapsed Ovarian Cancer

An Open-Label, Single-Arm, Phase II Study of IV Weekly (Days 1 and 8 Every 21 Days) HYCAMTIN in Combination With Carboplatin (Day 1 Every 21 Days) as Second-Line Therapy in Subjects With Potentially Platinum-Sensitive Relapsed Ovarian Cancer

This study was designed to find the most effective and safest doses of both HYCAMTIN and CARBOPLATIN that can be given for the treatment of ovarian cancer. This study may allow researchers to determine the effectiveness of combining HYCAMTIN and CARBOPLATIN.

Inclusion criteria:

• Subject must have baseline laboratory values as follows:
• Hemoglobin 9.0 g/dL
• Neutrophils 1,500/mm3
• Platelets 100,000/mm3
• Creatinine 1.5 mg/dL ( 133 mol/l) or creatinine clearance 60 mL/min
• Serum bilirubin < 2.0 mg/dL (< 35 umol/L)
• SGOT/AST, SGPT/ALT and alkaline phosphatase < 2 times ULN if liver metastases are absent by abdominal CT or MRI or < 5 times ULN if liver metastases are present
• Subject is allowed to have received, but is not required to have received, one additional prior non-cytotoxic regimen for management of recurrent or persistent disease according to the following definition: Non-cytotoxic (biologic or cytostatic) agents include (but are not limited to) monoclonal antibodies, cytokines, and small-molecule inhibitors of signal transduction
• Subject is female 18 years of age with an ECOG Performance Status of 0, 1 or 2
• Subject has recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer which was histologically confirmed at the time of the primary diagnosis
• Subject has received one prior platinum-based chemotherapeutic regimen (containing either carboplatin or cisplatin) for the treatment of primary disease. Consolidation chemotherapy is not permitted
• Subject's disease is considered potentially platinum-sensitive (i.e., have had a platinum-free interval following complete response to carboplatin or cisplatin of greater than 6 months)
• Subject must have at least one measurable lesion as determined by diagnostic studies including CT or MRI or physical exam. Measurable disease must be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be 20 mm in their longest dimension when measured by conventional techniques, including palpation, plain X-ray, CT and MRI, or 10 mm when measured by spiral CT. Palpable tumor masses that cannot be evaluated radiologically must have 2 diameters 20 mm. An attempt to document lesion size by ultrasound should be undertaken for palpable lesions not visualized on CT (or MRI).
• The same diagnostic imaging method used to evaluate disease must be used throughout the study to evaluate lesions consistently
• Stable blood, liver and renal functions.
• Subjects of child-bearing potential must be practicing adequate contraception (e.g. oral contraceptives, diaphragm plus spermicide, or IUD) for at least 3 months prior to study start. The same contraceptive method should be used throughout the study and continue for at least 4 weeks after the end of the study

Exclusion criteria:

• Pregnant or lactating.
• Subject has received more than 1 prior chemotherapy regimen or a history of consolidation cytotoxic chemotherapy
• Subject has concomitant or history of previous malignancies, with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease-free for 5 years
• Subject has brain metastases as documented by CT or MRI. Note: Asymptomatic subjects do not require CT or MRI to rule out brain metastases
• Received previous treatment with HYCAMTIN.
• Subject has received an investigational agent within 30 days or 5 half-lives (whichever is longer) prior to study entry
• Received prior radiation therapy for ovarian cancer