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About
This phase I clinical trial studies the safety and best dose of selumetinib and cixutumumab in treating patients with advanced solid malignancies. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor to grow and spread. Others find tumor cells and help kill them or carry [cancer/tumor]-killing substances to them.
Full description
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
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.
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Inclusion criteria
Exclusion criteria
Patient current evidence of active and uncontrolled infection, documented Child's class B-C cirrhosis, or active pancreatitis
Uncontrolled hypertension (BP > 150/95 despite optimal therapy)
Left ventricular ejection fraction of =< 45% or NYHA Class II-IV CHF
Prior or current cardiomyopathy
Atrial fibrillation with heart rate > 100 bpm
Unstable ischemic heart disease (myocardial infarction within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly)
Patients receiving any medications that are inhibitors or inducers of specific CYP450 enzyme(s) are ineligible
History of growth hormone deficiency or excess, or patient is concurrently using growth hormone (GH), or growth hormone inhibitors
Patient has a known hypersensitivity to the components of study drugs, its analogs, or drugs of similar chemical or biologic composition
Patient has prior exposure to IGF-1R or RAF/MEK inhibitors
The patient has poorly controlled diabetes mellitus, defined as a Hba1c > 7%
Patients with active CNS metastases and/or carcinomatous meningitis are excluded; however, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for 3 months prior to entry as defined as:
Patient with a primary central nervous system tumor
Patient has known psychiatric or substance abuse disorders that is uncontrolled and would interfere with cooperation with the requirements of the trial
Patient is pregnant or breastfeeding.
Patient is Human Immunodeficiency virus (HIV)-positive and on highly active antiretroviral therapy (HAART), as drug interactions between those agents and these experimental agents are wholly unknown; if this combination goes forward, this regimen will need to be tested in this group of patients in the future; patients with HIV who are well compensated and do not require HAART therapy are eligible for the study
Patient has active hepatitis B or C on treatment
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days of day 1 of therapy
Use of any other concurrent investigational agents or anticancer agents including hormonal therapy, except in the case of prostate cancer patients who are being treated with LHRH agonist at the time of trial entry
Patients should avoid excessive sun exposure and use adequate sunscreen protection if sun exposure is anticipated
History of any serious intraocular or retinal pathology as determined by the reference ophthalmologist, with the exception of controlled glaucoma or cataracts; in particular, patients with a history of retinal vein occlusion (RVC) or central serous retinopathy (CSR), or predisposing factors to RVO or CSR as assessed by ophthalmic exam (e.g. evidence of new optic disc cupping, new visual field defects, intraocular pressure > 21 mmHg, uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes) must be excluded
Primary purpose
Allocation
Interventional model
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30 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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