This phase I trial studies the side effects and the best dose of sunitinib malate in treating human immunodeficiency virus (HIV)-positive patients with cancer receiving antiretroviral therapy. Sunitinib malate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
PRIMARY OBJECTIVES: I. To determine the safety and to investigate the pharmacological interactions of administering sunitinib (sunitinib malate) in subjects with cancer who are also HIV positive on anti-retroviral regimens containing protease inhibitors and/or non-nucleoside reverse transcriptase inhibitors. SECONDARY OBJECTIVES: I. To evaluate the efficacy of sunitinib in treating non-acquired immunodeficiency syndrome (AIDS) defining cancers (NADCs) in these subjects. II. To detect alterations in antiretroviral drug pharmacokinetics due to sunitinib. III. To detect alterations in immune parameters, including total leukocyte count, cluster of differentiation (CD) 4 and viral load, during sunitinib therapy. IV. To correlate variations in genes involved in sunitinib absorption, metabolism, and elimination, including cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), cytochrome P450, family 3, subfamily A, polypeptide 5 (CYP3A5), ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1), and breast cancer resistance protein (ABCG2), with drug pharmacokinetics. V. To explore the potential for pharmacological interactions between sunitinib and newer antiretroviral agents such as integrase and chemokine (C-C motif) receptor 5 (gene/pseudogene) (CCR5) inhibitors. OUTLINE: This is a dose-escalation study. Patients receive sunitinib malate orally (PO) daily on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Jonsson Comprehensive Cancer Center
Los Angeles, California, United States
Lombardi Comprehensive Cancer Center at Georgetown University
Washington D.C., District of Columbia, United States
Northwestern University
Chicago, Illinois, United States
AIDS - Associated Malignancies Clinical Trials Consortium
Rockville, Maryland, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Washington University - Jewish
Saint Loius, Missouri, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Albert Einstein College of Medicine
The Bronx, New York, United States
Case Western Reserve University
Cleveland, Ohio, United States
Abramson Cancer Center of The University of Pennsylvania
Philadelphia, Pennsylvania, United States
...and 1 more locations
Grades 3, 4, and 5, treatment-related adverse events, graded according to the National Cancer Institute (NCI) CTCAE version 3.0
Results will be presented descriptively. Continuous data will be summarized for each cohort using descriptive statistics (N, mean, median, standard deviation, minimum, maximum, geometric mean, and % coefficient of variation \[CV\]).
Time frame: Up to 30 days after completion of study treatment
Dose-limiting toxicity (DLT) defined as an adverse event that is possibly related to the study medication, graded according to the NCI CTCAE version 3.0
Results will be presented descriptively. Continuous data will be summarized for each cohort using descriptive statistics (N, mean, median, standard deviation, minimum, maximum, geometric mean, and % coefficient of variation \[CV\]).
Time frame: 6 weeks
Evaluation of response
Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) (solid tumors), AIDS Clinical Trials Group (ACTG) (Kaposi's sarcoma \[KS\]), Cheson (lymphoma), Durie (multiple myeloma), or International Working Group for Response Criteria for acute leukemias criteria depending on the subject's primary disease.
Time frame: Up to 30 days after completion of study treatment
Antiretroviral drug pharmacokinetics due to sunitinib malate
Pharmacokinetic parameters within the individual groups will be compared using a Kruskall-Wallis test, Wilcoxon non-parametric test for paired data and Mann-Whitney test for unpaired data.
Time frame: At baseline and at 1, 2, 3, 4, 5, 6, 7, 8, and 24 hours of days 1and 2
Alterations in immune parameters, including total leukocyte count, CD4, and viral load
Time frame: Up to 30 days after completion of study treatment
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