Study of GPX-100 in the Treatment of Metastatic Breast Cancer
The purpose of this early Phase II multicenter trial is to determine the objective clinical response to GPX-100, an anthracycline similar to doxorubicin, in up to 40 patients with newly diagnosed metastatic breast cancer. GPX-100 is unique among anthracyclines because it is not converted to doxorubicinol during metabolism in the body. This metabolite has been shown to be a major cause of damage to the heart (cardiotoxicity) in laboratory studies. Eligible patients who are enrolled in this study will receive GPX-100 as a single agent at the beginning of as many as 8 three week long cycles of chemotherapy. Objective measurements of tumor response will be made by computed tomography (CT) scans.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II, Open Label, Non-Randomized, Efficacy and Safety Study of an Intravenous Formulation of the Anthracycline Analog, GPX-100, in the Treatment of Metastatic Breast Cancer|
- Efficacy: sum of complete responders and partial responders
- Safety: a decrease in cardiac ejection fraction by multigated acquisition (MUGA) scans
- Percent of eligible patients with progressive disease (PD)
- Percent of patients with stable disease (SD)
- Percent of patients with complete response (CR)
- Percent of patients with partial response (PR)
- Overall response (sum of CR, PR, and SD)
- Time to progression (TTP)
- Presence and severity of new electrocardiogram (ECG) abnormalities
- Presence and severity of myelosuppression (bone marrow suppression)
- Presence and severity of alopecia (hair loss)
- Presence and severity of stomatitis
- Presence and severity of nausea
- Presence and severity of vomiting
|Study Start Date:||March 2005|
|Estimated Study Completion Date:||November 2005|
Study Design - Two-stage, multicenter, open-label, non-randomized study with intravenous (IV) dose administration of GPX-100 and limited dose-escalation and de-escalation. After confirmation of the maximum tolerated dose (MTD) and interim analysis of efficacy and safety (Stage I), if necessary the study cohort will be enlarged to confirm the estimate of clinical efficacy (Stage II) using the established MTD.
Sample Size - 20 patients in Stage I and up to 20 patients in Stage II.
Dosage Form - IV solution of sterilized lyophilized powder in Sodium Chloride (NaCl) for Injection, USP (0.9%).
Doses - 140 mg/m2 GPX-100 with escalation to 170 mg/m2 and de-escalation to 105 mg/m2 depending upon clinical response and toxicity.
Administration - One IV infusion every 3 weeks for up to 8 doses.
Efficacy Parameters - Activity of GPX-100 will be evaluated in terms of measurable tumor response and disease progression according to RECIST criteria. Blood samples will be obtained for determination of pharmacokinetic parameters and the presence of doxorubicinol following the first dose of GPX-100.
Safety Parameters - Dose tolerance and treatment toxicity, especially cardiotoxicity, of GPX-100 will be evaluated. A baseline medical history including Karnofsky Performance Status and a physical examination, hematology profile (CBC, differential, platelet count), chemistry profile including electrolytes, serum calcium, liver and renal function tests, urinalysis, chest and abdominal CT scans, and a bone scan will be done. Interval history with adverse event (AE) assessment and performance status, physical examination, and hematology and clinical chemistry profile will be repeated every 3 weeks during treatment. In addition, hematology and chemistry profiles will be repeated weekly between treatment visits. Chest and abdominal CTs and bone scans will be repeated at 6-week intervals as appropriate for tumor assessment. An MRI of the brain will be performed at the baseline visit if clinically indicated. Urinalysis will be repeated at six-week intervals during treatment. Cardiotoxicity will be assessed with ECG and MUGA scans at baseline, every 6 weeks during treatment, and 6-8 weeks after the last dose of GPX-100. There will be continued follow-up at 6-8 week intervals if indicated by changing cardiac function until normal or stable. Treatment will be discontinued if there is objective disease progression or unacceptable treatment toxicity. A follow-up visit will occur 6-8 weeks after the last treatment visit for each patient, whether the study was completed per protocol or the patient discontinues study treatment early for any reason. The following evaluations will be performed at the follow-up visit: physical examination, adverse event assessment, ECG, MUGA scan, hematology and clinical chemistry profiles, and urinalysis. Serum pregnancy tests will be performed at baseline and at the follow-up visit, if necessary.
|United States, Utah|
|Huntsman Cancer Center, University of Utah|
|Salt Lake City, Utah, United States, 84112|
|University Hospital Queen Joanna|
|Sofia Cancer Center|
|Principal Investigator:||John H. Ward, MD||Hunstman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT|