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

Official Title

A Phase IB Study of the Combination of AZD6244 Hydrogen Sulfate (Selumetinib) and Cyclosporin A (CsA) in Patients With Advanced Solid Tumours With an Expansion Cohort in Metastatic Colorectal Cancer


This phase I/Ib trial studies the side effects and best dose of selumetinib when given together with cyclosporine in treating patients with solid tumours 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 tumour 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 tumour cells from growing. Giving selumetinib and cyclosporine may be a better treatment for solid tumours or colorectal cancer.

Trial Description

Primary Outcome:

  • 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
Secondary Outcome:
  • Incidence of adverse events that occur after course 1, day 1 assessed using NCI CTCAE version 4.0
  • Pharmacokinetic (PK) parameters, including the distribution of area under the curve and maximum concentration
  • Objective tumour response based on computed tomography scans (or magnetic resonance imaging if patients are allergic to iodinated contrast) per RECIST 1.1 criteria
  • Progression-free survival (PFS)
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 tumours. 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 tumours 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 Tumours [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.

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