Selumetinib and Cixutumumab in Treating Patients With Advanced Solid Malignancies
This phase I clinical trial studies the safety and best dose of selumetinib and cixutumumab in treating patients with advanced solid malignancies. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor to grow and spread. Others find tumor cells and help kill them or carry [cancer/tumor]-killing substances to them.
Adult Solid Neoplasm
Other: Pharmacological Study
Other: Laboratory Biomarker Analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I, Single-institution Open Label, Dose-escalation Trial With an Expansion Trial Cohort Evaluating the Safety and Tolerability of AZD6244 and IMCA12 in Subjects With Advanced Solid Malignancies|
- Maximum tolerated dose of selumetinib in combination with cixutumumab defined as the dose produced DLT in =< 1 out of 6 patients [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]The proportion of patients with serious or life threatening toxicities will be estimated along with 95% confidence intervals. Tabulated by dose combination, by toxicity type, and by the severity.
- The proportion of patients who experience PR, CR, or SD as defined by RECIST criteria [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]
- Pharmacokinetics of the combination of selumetinib and cixutumumab [ Time Frame: Prior to the dose and at 0.5, 1, 1.5, 2, 4, and 8 hours ] [ Designated as safety issue: No ]Peak serum level (Cmax), the trough level (Cmin), and the Area Under the serum concentration time Curve (AUC) will be summarized using descriptive statistics.
|Study Start Date:||November 2009|
|Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (selumetinib, cixutumumab)
Patients receive selumetinib PO BID on days 1-28 and cixutumumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Names:Biological: Cixutumumab
Other Names:Other: Pharmacological Study
Other Name: pharmacological studiesOther: Laboratory Biomarker Analysis
I. Determine the safety and toxicity of the combination of AZD6244 and IMC-A12 in advanced solid tumors that have progressed on standard therapy.
II. Finding the maximum tolerated dose (MTD)/recommended phase II dose of the combination.
I. Explore preliminary evidence of efficacy of the combination of AZD6244 and IMC-A12 in advanced solid tumors using RECIST criteria for tumor response.
II. Define pharmacodynamic (PD) profile of the combination of IMC-A12 and AZD6244.
III. Correlate pharmacokinetics (PK) of the combination of IMC-A12 and AZD6244 to pharmacodynamic (PD) endpoints.
IV. Assess the PK/PD (phospho-S6) link with AZD6244 when administered in combination with IMC-A12.
OUTLINE: This is a dose-escalation study of selumetinib and cixutumumab.
Patients receive selumetinib orally (PO) twice daily (BID) on days 1-28 and cixutumumab intravenously (IV) on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01061749
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator:||Nilofer Azad||Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center|