Clinical Trial: Sunitinib Malate in Treating HIV-Positive Patients With Cancer Receiving Antiretroviral Therapy

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 1/Pharmacokinetic Study of Sunitinib in Patients With Cancer Who Also Have HIV and Are on HAART Therapy

Brief Summary: 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.

Detailed Summary:

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.

Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Grades 3, 4, and 5, treatment-related adverse events, graded according to the National Cancer Institute (NCI) CTCAE version 3.0 [ Time Frame: Up to 30 days after completion of study treatment ]
    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]).
  • 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 [ Time Frame: 6 weeks ]
    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]).


Original Primary Outcome:

  • Safety
  • Pharmacological interactions


Current Secondary Outcome:

  • Evaluation of response [ Time Frame: Up to 30 days after completion of study treatment ]
    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.
  • Antiretroviral drug pharmacokinetics due to sunitinib malate [ Time Frame: At baseline and at 1, 2, 3, 4, 5, 6, 7, 8, and 24 hours of days 1and 2 ]
    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.
  • Alterations in immune parameters, including total leukocyte count, CD4, and viral load [ Time Frame: Up to 30 days after completion of study treatment ]


Original Secondary Outcome:

  • Efficacy
  • Alterations in antiretroviral drug pharmacokinetics due to sunitinib malate
  • Alterations in immune parameters, including total leukocyte count, CD4 count, and viral load, during treatment with sunitinib malate
  • Correlation of variations in genes involved in sunitinib malate absorption, metabolism, and elimination (e.g., CYP3A4, CYP3A5, ABCB1, and ABCG2) with drug pharmacokinetics


Information By: National Cancer Institute (NCI)

Dates:
Date Received: April 29, 2009
Date Started: August 2009
Date Completion:
Last Updated: March 14, 2014
Last Verified: September 2013