A Phase I Study of STA-5312 Administered Weekly in Subjects With Advanced or Metastatic Solid Tumors
18 Years
N/A
Both
Advanced or Metastatic Solid Tumors
Trial Information
A Phase I Study of STA-5312 Administered Weekly in Subjects With Advanced or Metastatic Solid Tumors
This is a Phase I open-label, dose-escalation safety study in subjects with refractory non
hematologic malignancies. STA-5312 will be administered intravenously. Administration is
anticipated to take 1 hour, although infusion time may be extended when appropriate with
large infusion volumes. A treatment cycle is 4 weeks with a weekly infusion of STA 5312 for
the first 3 weeks of each 4 week cycle. The planned treatment schedule is 2 cycles of
STA-5312 treatment (8 weeks). Decisions regarding dose escalation and DLT determination
will be made based on observations during the first cycle of therapy. Subjects who tolerate
treatment may be eligible to continue receiving additional cycles of STA 5312 per the
investigator’s medical judgment. Evaluation of antitumor response will be performed after
every 2 cycles of STA 5312 administration.
The initial dose level of STA 5312 will be 6 mg/m2. The starting dose level was chosen
based on preclinical animal studies that used alternate day dosing x 3/week on alternate
weeks. The dose level of 6 mg/m2 represents less than 1/10 the weekly dose (3 mg/m2 x 3)
that demonstrated severe toxicity. Subsequent dose escalations will follow an accelerated
titration design once the 8 mg/m2 cohort is completed No fewer than 3 patients will be
enrolled at each dose level. Once a DLT is observed the cohort will be expanded to at least
six subjects. If one-third of at least 6 subjects treated at a dose level experience a DLT,
dose escalation will terminate. The dose below this will be considered the MTD and will be
expanded to at least 12 subjects to collect additional safety and pharmacokinetic data. No
intrasubject dose escalations will occur.
Inclusion Criteria:
- Male and female subjects aged at least 18 years with histologically-confirmed non
hematological malignancy that is metastatic or unresectable and for which no standard
therapy exists.
- Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2.
- Peripheral neuropathy less than Grade 2 on National Cancer Institute Common Toxicity
Criteria (NCI CTC) version 3 adverse event scale.
- Subjects must have acceptable organ and marrow function during the Screening Period
as defined below. (Note: Subjects must meet these criteria at each pre-dose visit
to receive additional doses of STA-5312).
- Absolute neutrophil count (ANC) greater than 1500 cells/µL
- Platelets greater than 100,000/µL
- Total bilirubin must be <1.5 times ULN
- Aspartate transaminase (AST) ≤3 times ULN or less than 5 times the ULN in
subjects with liver metastases
- Alanine transaminase (ALT) ≤3 times ULN or less than 5 times the ULN in subjects
with liver metastases
- Adequate renal function (serum creatinine <2.0 mg/dL).
- Electrocardiogram (ECG) without evidence of clinically significant ventricular
arrhythmias or active ischemia as determined by the investigator.
- Documented cardiac ejection fraction greater than 50% obtained within 30 days of
administration of the first dose.
- The effects of STA-5312 on the developing human fetus are unknown. Therefore, women
of childbearing potential (defined as women over 50 years of age or history of
amenorrhea for <12 months prior to study entry) must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry and for the duration of study participation. Should a female subject
become pregnant or suspect she is pregnant while participating in this study, she
should inform the treating physician immediately.
- Ability to understand and willingness to sign a written informed consent document.
Exclusion Criteria:
- Women who are pregnant or breast-feeding.
- Subjects who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study
- Subjects with previous high-dose chemotherapy with autologous allogeneic
hematopoietic stem cell transplantation.
- Subjects with primary brain tumors or active brain metastases are excluded. Subjects
with previously treated brain metastases who are not receiving corticosteroids or
anticonvulsants are eligible.
- History of stroke within 6 months of treatment or other significant neurological
limitations.
- Use of any investigational agents within 4 weeks of study enrollment.
- History of severe allergic reactions to excipients (e.g. Tween 80/polysorbate 80),
including severe hypersensitivity reactions defined as greater than Grade 3 based on
NCI CTC version 3.
- Uncontrolled intercurrent illness including, but not limited to, human
immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral
therapy, ongoing or active infection, symptomatic congestive heart failure, unstable
angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations
that would limit compliance with study requirements.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Authority:
United States: Food and Drug Administration
Study ID:
5312-02
NCT ID:
NCT00276913
Start Date:
June 2004
Completion Date:
Related Keywords:
- Advanced or Metastatic Solid Tumors
- Neoplasms
Name | Location |
|---|---|
| Steven Limentani, MD | Charlotte, North Carolina 28203 |
