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
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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Efficacy: sum of complete responders and partial responders
John H. Ward, MD
Hunstman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT
United States: Food and Drug Administration
|Huntsman Cancer Center, University of Utah||Salt Lake City, Utah 84112|