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
14 other identifiers
interventional
40
2 countries
10
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Aug 2014
Longer than P75 for phase_1
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 10, 2014
CompletedFirst Posted
Study publicly available on registry
July 11, 2014
CompletedStudy Start
First participant enrolled
August 29, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
April 26, 2019
CompletedFebruary 11, 2025
February 1, 2025
2.4 years
July 10, 2014
February 8, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
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
The maximum tolerated dose will be defined as the highest dose in which 0 or 1 out of 6 patients have a DLT.
28 days
Secondary Outcomes (4)
Incidence of adverse events that occur after course 1, day 1 assessed using NCI CTCAE version 4.0
Up to 30 days after completion of study treatment
Pharmacokinetic (PK) parameters, including the distribution of area under the curve and maximum concentration
Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours on days -7, -3, and 1 of course 1
Objective tumor response based on computed tomography scans (or magnetic resonance imaging if patients are allergic to iodinated contrast) per RECIST 1.1 criteria
Up to 30 days after completion of study treatment
Progression-free survival (PFS)
From first therapy received to documented disease progression or death from any cause, assessed up to 30 days after completion of study treatment
Other Outcomes (1)
Change in expression of phosphorylated-mitogen-activated protein kinase 1
Baseline to up to 56 days
Study Arms (1)
Treatment (selumetinib and cyclosporine)
EXPERIMENTALPatients 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.
Interventions
Given PO
Given PO
Eligibility Criteria
You may qualify if:
- Before any study procedures are performed, subjects will have the details of the study described to them, and they will be given a written informed consent document to read; then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of study personnel
- DOSE ESCALATION PHASE: Histological or cytopathological diagnosis of an advanced cancer that is refractory to standard therapy or for which no standard therapy exists
- COHORT EXPANSION PHASE: Histological or cytopathological diagnosis of advanced/metastatic unresectable colorectal cancer with known rat sarcoma viral oncogene homolog (RAS) mutational status; patients with known B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations will not be eligible for the expansion cohort; all patients must have received and progressed or be intolerant of an oxaliplatin-containing regimen and an irinotecan-containing regimen
- COHORT EXPANSION PHASE: At least one tumor lesion amenable to core needle biopsy without unacceptable risk of a major procedural complication (one pretreatment and at least one on-treatment biopsy will be performed)
- COHORT EXPANSION PHASE: Patient must have measurable lesions as defined by RECIST version 1.1 criteria
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Estimated life expectancy \> 3 months
- Absolute neutrophil count (ANC) \>= 1,500/mcl
- Platelets \>= 100,000/mcl
- Hemoglobin \>= 9 g/dl
- Estimated glomerular filtration rate (eGFR) greater than or equal to 60 ml/min/1.73 m\^2
- Serum total bilirubin \< 1.5 x upper limit or normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]), alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN; if liver involvement, AST, ALT =\< 5.0 x ULN
- Alkaline phosphatase =\< 2.5 x ULN; if liver involvement, alkaline phosphatase =\< 5.0 x ULN
- Serum albumin \>= 2.5 g/dl
- +4 more criteria
You may not qualify if:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients who are receiving any other investigational agents
- Prior full field radiotherapy \< 4 weeks or limited field radiotherapy \< 2 weeks prior to first study drug administration
- Patients with brain metastases may participate in this trial provided they are clinically stable; patients who are \< 1 month from definitive therapy, receiving steroid therapy or taper, or anti-convulsant medications (started for brain metastases) must not be included
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244 or cyclosporine A or their excipients
- Patients with a history of thrombotic or embolic events within the last six months such as a cerebrovascular accident (including transient ischemic attacks), pulmonary embolism
- Cardiac conditions as follows:
- Active coronary artery disease, unstable or newly diagnosed angina or myocardial infarction less than 12 months prior to first study drug administration
- Class II-IV New York Heart Association (NYHA) congestive heart failure
- Uncontrolled hypertension (systolic blood pressure \[BP\] \> 150 mmHg and diastolic BP \> 90 mmHg for 24 hours) despite optimal medical management; blood pressure must be below 140/90 mmHg at screening; subjects with a history of hypertension who are receiving treatment with calcium channel blockers that are cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates should be changed to an alternative antihypertensive medication prior to first study drug administration
- Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
- Corrected QT (QTc) (Frederica) prolongation \> 480 msec
- Subjects with valvular heart disease Common Terminology Criteria for Adverse Events (CTCAE) (version 4.0) grade 2
- Known left ventricular ejection fraction (LVEF) \< 50%
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris (Canadian Cardiovascular Society grade II-IV despite medical therapy), cardiac arrhythmia, active bleeding diatheses, or psychiatric illness/social situations that would limit compliance with study requirements
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Christopher H Lieu
University of Texas MD Anderson Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 10, 2014
First Posted
July 11, 2014
Study Start
August 29, 2014
Primary Completion
January 31, 2017
Study Completion
April 26, 2019
Last Updated
February 11, 2025
Record last verified: 2025-02