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

Solid Tumor Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00085878
• Other study ID #: 485232/002
• Secondary ID: 002
• Status: Completed
• Phase: Phase 1
• First received: June 16, 2004
• Last updated: October 15, 2008
• Start date: January 2003

Study information

• Verified date: October 2008
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumor Cancer

Intervention

Drug:
• SB-485232

Locations

Country	Name	City	State
United States	GSK Investigational Site	Durham	North Carolina
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	- 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	- 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