Selumetinib and Cyclosporine in Treating Patients With Advanced Solid Tumors or Advanced or Metastatic Colorectal Cancer
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|ClinicalTrials.gov Identifier: NCT02188264|
Recruitment Status : Active, not recruiting
First Posted : July 11, 2014
Last Update Posted : May 5, 2020
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Colorectal Carcinoma Solid Neoplasm Stage IIIA Colorectal Cancer AJCC v7 Stage IIIB Colorectal Cancer AJCC v7 Stage IIIC Colorectal Cancer AJCC v7 Stage IVA Colorectal Cancer AJCC v7 Stage IVB Colorectal Cancer AJCC v7||Drug: Cyclosporine Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Selumetinib||Phase 1|
I. To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combination of AZD6244 (selumetinib) and cyclosporin A (cyclosporine) in adult patients with advanced solid tumors.
I. To determine the safety profile and tolerability of this regimen in this patient population.
II. To determine the pharmacokinetics of the combination. III. To evaluate the selected biomarkers of drug effect in patients with advanced solid tumors or refractory metastatic colorectal cancer (CRC).
IV. Evaluate the activity of the combination in terms of objective response rate (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1), progression-free survival (PFS).
OUTLINE: This is a phase I, dose-escalation study of selumetinib followed by a phase Ib study.
Patients receive selumetinib orally (PO) twice daily (BID) on day -7 of course 1 and then on days 1-28 (one dose on day 1 only). Patients also receive cyclosporine PO BID on day -3 of course 1 and then on days 1-28 (one dose on day 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase IB Study of the Combination of AZD6244 Hydrogen Sulfate (Selumetinib) and Cyclosporin A (CsA) in Patients With Advanced Solid Tumors With an Expansion Cohort in Metastatic Colorectal Cancer|
|Actual Study Start Date :||August 5, 2014|
|Actual Primary Completion Date :||January 31, 2017|
Experimental: Treatment (selumetinib and cyclosporine)
Patients receive selumetinib PO BID on day -7 of course 1 and then on days 1-28 (one dose on day 1 only). Patients also receive cyclosporine PO BID on day -3 of course 1 and then on days 1-28 (one dose on day 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Incidence of DLT defined as any grade 3 non-hematological toxicity or grade 4 hematological toxicity attributed to selumetinib or cyclosporine graded per National Cancer Institute (NCI) CTCAE version 4.0 [ Time Frame: 28 days ]The maximum tolerated dose will be defined as the highest dose in which 0 or 1 out of 6 patients have a DLT.
- Incidence of adverse events that occur after course 1, day 1 assessed using NCI CTCAE version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ]Adverse events will be tabulated by type and grade.
- Pharmacokinetic (PK) parameters, including the distribution of area under the curve and maximum concentration [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours on days -7, -3, and 1 of course 1 ]Looking at historical data on patients previously treated on single-agent therapy, the distribution of these PK parameters will be estimated in patients treated with single-agent selumetinib and single-agent cyclosporine. The distribution of these parameters in the combination study will be qualitatively compared to the single-agent distribution.
- Objective tumor response based on computed tomography scans (or magnetic resonance imaging if patients are allergic to iodinated contrast) per RECIST 1.1 criteria [ Time Frame: Up to 30 days after completion of study treatment ]Analysis of efficacy measures will be descriptive. Antitumor activity of the combination of selumetinib and cyclosporine will be based on the best overall response. Response rate (complete response [CR], partial response [PR], CR + PR) will be tabulated with 95% exact binomial confidence intervals. If applicable, response rate will also be tabulated by patients' baseline gene mutation status (eg, KRAS and BRAF). Data listings will present disease response category (eg, CR, PR, stable disease), duration of response, and as appropriate, tumor marker measurements.
- Progression-free survival (PFS) [ Time Frame: From first therapy received to documented disease progression or death from any cause, assessed up to 30 days after completion of study treatment ]PFS will be estimated using the product-limit method of Kaplan and Meier.
- Change in expression of phosphorylated-mitogen-activated protein kinase 1 [ Time Frame: Baseline to up to 56 days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02188264
|United States, California|
|University of California Davis Comprehensive Cancer Center|
|Sacramento, California, United States, 95817|
|United States, Colorado|
|University of Colorado Hospital|
|Aurora, Colorado, United States, 80045|
|United States, Missouri|
|Siteman Cancer Center at West County Hospital|
|Creve Coeur, Missouri, United States, 63141|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey|
|New Brunswick, New Jersey, United States, 08903|
|United States, North Carolina|
|UNC Lineberger Comprehensive Cancer Center|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|United States, Pennsylvania|
|University of Pittsburgh Cancer Institute (UPCI)|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|University Health Network-Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Christopher H Lieu||University of Texas MD Anderson Cancer Center LAO|