NCT02188264

Selumetinib and Cyclosporine in Treating Patients With Advanced Solid Tumors or Advanced or Metastatic Colorectal Cancer

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/Ib trial studies the side effects and best dose of selumetinib when given together with cyclosporine in treating patients with solid tumors or colorectal cancer that have spread to other places in the body and cannot be cured or controlled with treatment. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as cyclosporine, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop tumor cells from growing. Giving selumetinib and cyclosporine may be a better treatment for solid tumors or colorectal cancer.

Detailed description

PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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.

Conditions

• 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

Interventions

Type	Name	Description
DRUG	Cyclosporine	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies
DRUG	Selumetinib	Given PO

Timeline

• Start date: 2014-08-29
• Primary completion: 2017-01-31
• Completion: 2019-04-26
• First posted: 2014-07-11
• Last updated: 2025-02-11

Locations

10 sites across 2 countries: United States, Canada