A Phase I, Dose Escalation Study to Assess the Safety and Pharmacokinetics of SB- 485232 Administered as Daily Subcutaneous Injections in Adult Patients With Solid Tumors

Dose-Escalation Study Of SB-485232 Administered As Daily Subcutaneous Injections In Adults With Solid Tumors

Sponsors

Lead sponsor: GlaxoSmithKline

Source GlaxoSmithKline
Brief Summary

This is a phase I, open-label, dose-escalation study of SB-485232. Subjects will receive SB-485232 administered as subcutaneous injections daily for 14 days. Dose escalation (enrollment into the next cohort) cannot occur until all three subjects have completed the previous cohort; 5 doses will be tested. An additional dosing regimen has been added to evaluate higher doses given twice weekly for 7 weeks. Therefore, the full evaluation period for each patient will extend out to approximately eleven weeks after the first day of SB-485232 dosing.

Overall Status Completed
Start Date January 2003
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
- Safety and tolerability endpoints will include evaluation of adverse events and changes in laboratory values and clinical variables from pre-dose values. 11 Weeks
Secondary Outcome
Measure Time Frame
- Biologically effective dose based. - Pharmacokinetic endpoints: AUC, Adverse Events, cmax, tmax, and t1/2. - Presence or absence of anti-SB-485232 antibodies. - Pharmacodynamic endpoints. - Radiographic tumor assessments. 11 Weeks
Enrollment 25
Condition
Intervention

Intervention type: Drug

Intervention name: SB-485232

Eligibility

Criteria:

Inclusion Criteria:

- Histologically or cytologically confirmed diagnosis of malignancy.

- Subjects with solid tumors must have locally advanced or metastatic disease at the time of enrollment.

- Measurable or evaluable disease that is refractory or resistant to standard therapy or for which there is no effective standard therapy.

- Predicted life expectancy of at least 12 weeks.

- Kinesin spindle protein (KPS) of greater than 70%.

- No chemotherapy, immunotherapy, hormonal therapy, or biological therapy for cancer, radiotherapy, or surgical procedures (except for minor surgical procedures) within 4 weeks before beginning treatment with SB-485232 (6 weeks for nitrosoureas and mitomycin C).

- Subjects must have recovered from toxicities (incurred as a result of previous therapy) sufficiently to be entered into a Phase I study.

- Provide written informed consent.

- Absence of anti-SB-485232 antibodies.

- Hemoglobin greater than or equal to 9 g/dL.

- Absolute neutrophil count greater than or equal to 1.5 X 109 /L.

- Platelet count greater than or equal to 100 X 109 /L.

- Partial thromboplastin time (PTT) and prothrombin time/international normalized ratio (PT/INR) within normal limits.

- Serum creatinine less than or equal to 1.5 mg/dL (135 µmol/L) or estimated creatinine clearance greater than 50 mL/min (calculated by the Cockcroft-Gault Formula).

- Total serum bilirubin less than or equal to 1.5 mg/dL.

- Aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal to 3 X ULN.

- Sexually active males or females of reproductive capacity must use adequate contraception.

- For subjects with a history of coronary artery disease, stress test must be within normal limits.

- Subjects with a history of congestive heart failure, myocardial infarction or prior anthracycline chemotherapy must have a Multiple Gated Acquisition (MUGA) scan with a left ventricular ejection fraction of greater than 40%.

Exclusion Criteria:

- Women who are pregnant or are breast-feeding.

- Severe or uncontrolled infections requiring systemic antibiotic therapy.

- Any serious medical or psychiatric disorder that would interfere with subject safety or informed consent.

- Known leptomeningeal disease or evidence of prior or current metastatic brain disease.

- Receiving concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy.

- Receiving concurrent systemic steroids.

- History of ventricular arrhythmias requiring drug or device therapy.

- Any severe concurrent disease or condition, including significant autoimmune diseases, which in the judgment of the principal investigator, would make the subject inappropriate for study participation.

- Any unresolved or unstable serious toxicity from prior administration of another investigational drug.

- Any investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of SB-485232.

- Psychological, familial, sociological, or geographical conditions that do not permit compliance with the study.

- Received prior treatment with SB-485232.

- Poor venous access.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
GSK Clinical Trials, MD Study Director GlaxoSmithKline
Location
facility
GSK Investigational Site | Santa Monica, California, 90404-2104, United States
GSK Investigational Site | Indianapolis, Indiana, 46202, United States
GSK Investigational Site | Durham, North Carolina, 27705, United States
GSK Investigational Site | Philadelphia, Pennsylvania, 19111, United States
Location Countries

United States

Verification Date

October 2008

Responsible Party

Name title: Study Director

Organization: GSK

Keywords
Condition Browse
Study Design Info

Allocation: Non-Randomized

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov