Selumetinib and Cixutumumab in Treating Patients With Advanced Solid Malignancies
|ClinicalTrials.gov Identifier: NCT01061749|
Recruitment Status : Completed
First Posted : February 3, 2010
Last Update Posted : January 25, 2016
|Condition or disease||Intervention/treatment||Phase|
|Adult Solid Neoplasm||Biological: Cixutumumab Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Selumetinib||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 IMC-A12 in Subjects With Advanced Solid Malignancies|
|Study Start Date :||November 2009|
|Actual Primary Completion Date :||April 2013|
|Actual Study Completion Date :||September 2014|
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: Laboratory Biomarker Analysis
Other: Pharmacological Study
- 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 ]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.
- 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 ]Peak serum level (Cmax), the trough level (Cmin), and the Area Under the serum concentration time Curve (AUC) will be summarized using descriptive statistics.
- 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 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01061749
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator:||Nilofer Azad||Johns Hopkins University/Sidney Kimmel Cancer Center|