Doxil Topotecan Doublet Cancer Study

• Status: Completed
• Trial end date: 2008-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective is to determine the nature and degree of the toxicity of weekly dosing of topotecan in escalating dose levels by cohorts of 3-6 patients in combination with a fixed dose of pegylated liposomal doxorubicin (Doxil).

The secondary objective is to determine the activity of weekly topotecan and pegylated liposomal doxorubicin in advanced solid tumors.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Christiana Care Health Services
• Collaborators: GlaxoSmithKline; Johnson & Johnson
• Treatments: Doxorubicin; Liposomal doxorubicin; Topoisomerase I Inhibitors; Topotecan

Criteria

Inclusion Criteria:

• ECOG functional status of 2 or better is required.

• The patient should be able to provide informed consent.

• Prior treatment with Doxil or topotecan is not permitted.

• Prior treatment with doxorubicin is permitted if the total dose was 350 mg/m2 or less. Prior treatment with epirubicin is permitted if the total dose was 560 mg/m2.

• Patients with controlled brain metastases will be considered eligible for therapy (i.e. metastases surgically removed; or irradiated metastases with stable neurologic function).

• Patients must have measurable disease (the presence of at least one measurable lesion).

• If previously irradiated lesions are to be used to measure response, documented growth of the lesions must have been observed following completion of radiation therapy.

• Patients must have a life expectancy of at least four weeks.

• Hematologic criteria: patients must have absolute neutrophil count (ANC) of 1200 or better; platelet count of 100,000/mm3 or better; hemoglobin (Hgb) ≥ 9.0g/dL.

• Hepatic criteria: bilirubin must be less than or equal to 1.7. SGOT, SGPT may be up to 2 x institutional upper limit of normal (ULN) but with the presence of liver metastasis the SGOT, SGPT may be up to 3 x institutional ULN.

• Serum creatinine must be < 1.5 mg/dl x ULN

• Patients with reproductive potential must use an adequate contraceptive method (e.g., abstinence, intrauterine device, oral contraceptives, barrier device with spermicide or surgical sterilization) during treatment and for three months after completing treatment.

• Patients must have a multigated acquisition (MUGA) scan or 2-d echocardiogram indicating an ejection fraction of ≥ 50% within 42 days prior to first dose of study drug. The method used at baseline must be used for later monitoring.

Exclusion Criteria:

• Patients with concurrent severe medical problems unrelated to malignancy, which would limit full compliance to the study or expose the patient to extreme risk with decreased life expectancy, are ineligible.

• Patients with previous or concomitant malignancy other than curatively treated carcinoma in situ of the cervix, basal cell or squamous cell carcinoma of the skin, or other primary cancer completely resected or treated within five years are ineligible. Exceptions are patients who have had tumors treated with no evidence of active disease who are felt by both the enrolling physician and the principal investigator (PI) to have a risk of relapse of less than 30%.

• Pregnant or lactating women.

• History of hypersensitivity reactions attributed to a conventional formulation of doxorubicin hydrochloride (HCL) or the components of Doxil®.

• History of cardiac disease with New York Heart Association Class III or greater, or clinical evidence of congestive heart failure.