Intravenous Weekly Topotecan In Subjects With Recurrent Or Persistent Endometrial Cancer

An Open-label, Phase II, Multicenter Study of Intravenous Weekly Topotecan in Subjects With Recurrent or Persistent Endometrial Cancer

The purpose of this study is to find out if Hycamtin given weekly is safe and effective for treating your endometrial cancer.

Inclusion Criteria:

• A subject will be eligible for inclusion in this study only if all of the following criteria are met:

• Subject has provided a written informed consent.

• Subject must be female and ≥18 years of age.

• Subjects' original endometrial carcinoma (any histologic type) must have had pathologic confirmation.

• Subject must have recurrent or persistent endometrial cancer.

• Subject must have at least one measurable lesion according to GOG-modified RECIST criteria.

  • Measurable disease must be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be ≥ 20 mm when measured by conventional techniques, including palpation, plain X-ray, CT and MRI, or ≥10 mm when measured by spiral CT.
  • Measurable disease found on chest X-ray must be confirmed with CT or MRI. Either CT or MRI must be used throughout the study to further evaluate these lesions.
  • The same diagnostic method (CT, MRI, X-ray or physical exam) used to evaluate disease, must be used throughout the study to consistently evaluate lesions.
  • Palpable tumor masses that cannot be evaluated by CT or MRI scan should be evaluated by ultrasound or confirmed by biopsy.
  • Evaluable disease (measurable or non-measurable) may be in a field of prior radiation provided that at least six weeks have elapsed since receiving radiation and disease progression is clearly documented by radiographic study. It is preferential for the target lesion to be located outside an irradiated field.
  • Non-measurable disease is defined as all other lesions, including small lesions (longest diameter <20 mm with conventional techniques or <10 mm with spiral CT scan).

• Subject has received one prior chemotherapy regimen (excluding all topoisomerase I inhibitors e.g., HYCAMTIN and irinotecan).

• 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. UM2004/00031/00 CONFIDENTIAL HCT100414 20

• Subject is at least 21 days from prior chemotherapy and at least 30 days from prior non-cytotoxic therapy and is recovered from associated toxicities.

• Subject must not have received radiotherapy for at least seven days.

• Subject must be at least three weeks since last major surgery (a lesser period is acceptable if deemed in the best interest of the subject). Subject must have an ECOG Performance Status of 0 or 1 (refer to

• Appendix 4, ECOG Performance Status).

• Subject must have, at screening, a probable life expectancy of at least three months.

• Subject of childbearing potential must be practicing adequate contraception [e.g., oral contraceptives, diaphragm plus spermicide, or intrauterine device (IUD)] or show documented complete abstinence from intercourse for at least three months prior to study start. The same contraceptive method should be used throughout the study and continue for at least four weeks after the end of the study. A subject will be considered of childbearing potential if not surgically sterile or post-menopausal (i.e., documented absence of menses for one year prior to entry into the study).

  14. Subject must have screening laboratory criteria as follows:

  • Hemoglobin ≥ 9.0 g/dL.
  • Neutrophils ≥ 1,500/mm³ [≥1.5 x 10^9/L].
  • Platelets ≥ 100,000/mm³ [≥100.0 x 10^9/L].
  • Creatinine ≤ upper limit of normal (ULN) or creatinine clearance (Clcreat) ≥ 60mL/min.
  • Creatinine clearance should be calculated using the Cockcroft-Gault formula:

Clcreat (mL/min) = (140-age [yr] x body wt [kg] x 0.85 72 x serum creatinine [mg/dL] OR Clcreat (mL/min) = 1.05 x (140-age [yr] x body wt [kg] serum creatinine [μmol/L]

• Serum bilirubin within normal limits.
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase < 2xULN if liver metastases are absent by abdominal CT or MRI or < 5xULN if liver metastases are present.

Exclusion Criteria:

A subject will not be eligible for inclusion in this study if any of the following criteria are met:

• Subject is pregnant or lactating.
• Subject has received more than one prior chemotherapy regimen. UM2004/00031/00 CONFIDENTIAL HCT100414 21
• 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 five years.
• Subject has active uncontrolled infection.
• Subject has brain metastases as documented by CT or MRI. Note: Asymptomatic subjects do not require CT or MRI to rule out brain metastases.
• Subject has received prior treatment with HYCAMTIN.
• Subject has a history of an allergic reaction to compounds chemically-related to HYCAMTIN or its constituents.
• Subject has received any investigational agent within 30 days or five half-lives (whichever is longer) prior to study entry.