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

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00890747
Collaborator
(none)
42
11
1
3.8

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: sunitinib malate
  • Other: pharmacological study
  • Other: laboratory biomarker analysis
Phase 1

Detailed Description

PRIMARY OBJECTIVES:
  1. 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:
  1. To evaluate the efficacy of sunitinib in treating non-acquired immunodeficiency syndrome (AIDS) defining cancers (NADCs) in these subjects.

  2. To detect alterations in antiretroviral drug pharmacokinetics due to sunitinib.

  3. To detect alterations in immune parameters, including total leukocyte count, cluster of differentiation (CD) 4 and viral load, during sunitinib therapy.

  4. 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.

  5. 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 Design

Study Type:
Interventional
Actual Enrollment :
42 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/Pharmacokinetic Study of Sunitinib in Patients With Cancer Who Also Have HIV and Are on HAART Therapy
Study Start Date :
Aug 1, 2009
Actual Primary Completion Date :
May 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (sunitinib malate)

Patients receive sunitinib malate PO daily on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Drug: sunitinib malate
Given PO
Other Names:
  • SU11248
  • sunitinib
  • Sutent
  • Other: pharmacological study
    Correlative studies
    Other Names:
  • pharmacological studies
  • Other: laboratory biomarker analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Grades 3, 4, and 5, treatment-related adverse events, graded according to the National Cancer Institute (NCI) CTCAE version 3.0 [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]).

    2. 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 [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]).

    Secondary Outcome Measures

    1. Evaluation of response [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.

    2. Antiretroviral drug pharmacokinetics due to sunitinib malate [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.

    3. Alterations in immune parameters, including total leukocyte count, CD4, and viral load [Up to 30 days after completion of study treatment]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Biopsy-proven solid tumor or hematological malignancy, including:

    • Metastatic renal cell carcinoma

    • A solid tumor malignancy, including an NADC or an AIDS-defining malignancy, if the subject has progressed following standard therapy and/or other curative options are not available

    • A hematologic malignancy, except for blast-phase leukemia, for which effective standard therapy or other curative options are not available

    • Serologic documentation of HIV infection at any time prior to study entry, as evidenced by positive enzyme linked immunosorbent assay (ELISA), positive western blotting (Western Blot), or other federally approved licensed HIV test, or a detectable blood level of HIV ribonucleic acid (RNA), or a positive anti-HIV antibody test

    • On stable anti-retroviral therapy for at least 4 weeks with a protease inhibitor (PI)-based or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen of at least three drugs, with no intention to change the regimen within 8 weeks after starting study drug

    • Patients who are on NNRTI and ritonavir PI-based therapy are eligible and will be enrolled in the ritonavir PI-based group (Group 3)

    • Patients who are on NNRTI and non-ritonavir PI-based therapy are eligible and will be enrolled in the non-ritonavir PI-based group (Group 2); NOTE: accrual to Group 2 will be closed upon approval of version 7.0 of the protocol

    • Patients who are on a highly active antiretroviral therapy (HAART) combination that includes neither a PI nor a NNRTI agent are eligible and will be enrolled in the NNRTI-based group (Group 1)

    • CD4 count > 50 cells/uL

    • Karnofsky performance status > 60%

    • Women of child-bearing potential must have a negative pregnancy test within 7 days before initiation of study drug dosing; post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential; male and female subjects of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug; (Note: a woman of childbearing potential is one who is biologically capable of becoming pregnant; this includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives)

    • Hemoglobin >= 8.0 gm/dL

    • Absolute neutrophil count (ANC) >= 1500 cells/mm^3

    • Platelet count >= 100,000 /mm^3

    • Creatinine within institutional normal limits or glomerular filtration rate (GFR) > 60 mL/min/m^2 (calculated by the Cockcroft-Gault equation), calculated as follows:

    • For males = (140 - age[years]) x (body weight [kg])/ (72) x (serum creatinine [mg/dL])

    • For females = 0.85 x male value

    • Total bilirubin should be =< 1.5 times upper limit of normal (ULN); if, however, the elevated bilirubin is felt to be secondary to indinavir therapy, then subjects will be allowed on protocol if total bilirubin =< 3.5 mg/dL, provided that the direct bilirubin is =< 1.5 times ULN; if the elevated bilirubin is felt to be secondary to atazanavir therapy, then subjects will be allowed on protocol without any limit on the total bilirubin if the direct bilirubin is =< 1.5 times ULN

    • Aspartate transaminase AST (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase ALT (serum glutamate pyruvate transaminase [SGPT]) < 2.5 times the ULN; unless subjects have liver metastases, in which case both AST and ALT must be =< 5 times ULN

    • Life expectancy of 3 months or more

    • Ability and willingness to give informed consent

    • Subjects must in the opinion of the Investigator be capable of complying with this protocol

    Exclusion Criteria:
    • Concurrent active opportunistic infection (OI)

    • Acute treatment for an infection or other serious medical illness within 14 days prior to study entry

    • Receipt of antineoplastic therapy, including investigational drug or standard treatment, within 2 weeks of study entry; must be able to demonstrate adequate recovery from prior therapy-related toxicities

    • Major surgery or radiation within 3 weeks prior to study entry

    • Concurrent treatment with medications, other than antiretroviral drugs used to treat HIV infection, that are known to inhibit or induce CYP3A4

    • Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease

    • Clinically significant cardiovascular disease, including uncontrolled hypertension (diastolic blood pressure >= 100 mmHg despite optimal medical therapy) or unstable angina

    • A myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, transient ischemic attack, or pulmonary embolism within 6 months of study entry

    • Abnormal left ventricular ejection fraction per institutional standards

    • Ongoing ventricular cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) grade >= 2

    • Subjects with a history of serious ventricular arrhythmia (ventricular tachycardia [VT] or ventricular fibrillation [VF] >= 3 beats in a row)

    • Serious cardiac arrhythmia requiring medication

    • QTc interval > 500 msec

    • Psychiatric illness that would limit compliance with study requirements

    • Pre-existing thyroid abnormality that cannot be maintained with medication to keep measures of thyroid stimulating hormone within the normal range

    • Female subjects who are pregnant or breast-feeding

    • Another severe and/or life-threatening medical disease

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Jonsson Comprehensive Cancer Center Los Angeles California United States 90095
    2 Lombardi Comprehensive Cancer Center at Georgetown University Washington District of Columbia United States 20057
    3 Northwestern University Chicago Illinois United States 60611
    4 AIDS - Associated Malignancies Clinical Trials Consortium Rockville Maryland United States 20850
    5 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
    6 Washington University - Jewish Saint Loius Missouri United States 63110
    7 Albert Einstein College of Medicine Bronx New York United States 10461
    8 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    9 Case Western Reserve University Cleveland Ohio United States 44106
    10 Abramson Cancer Center of The University of Pennsylvania Philadelphia Pennsylvania United States 19104
    11 Virginia Mason Medical Center Seattle Washington United States 98101

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: John Deeken, AIDS Associated Malignancies Clinical Trials Consortium

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00890747
    Other Study ID Numbers:
    • NCI-2012-02208
    • NCI-2012-02208
    • AMC-061
    • AMC-061
    • U01CA121947
    • NCT01727102
    First Posted:
    Apr 30, 2009
    Last Update Posted:
    Mar 17, 2014
    Last Verified:
    Sep 1, 2013
    Keywords provided by National Cancer Institute (NCI)
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 17, 2014