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Sunitinib Malate in Treating HIV-Positive Patients With Cancer Undergoing Highly Active Antiretroviral Therapy
This study is not yet open for participant recruitment.
Verified by National Cancer Institute (NCI), April 2009
First Received: April 29, 2009   No Changes Posted
Sponsors and Collaborators: AIDS Associated Malignancies Clinical Trials Consortium
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00890747
  Purpose

RATIONALE: Sunitinib malate may stop the growth of cancer cells by blocking blood flow to the cancer and by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects of sunitinib malate in treating HIV-positive patients with cancer undergoing highly active antiretroviral therapy.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Kidney Cancer
Leukemia
Lymphoma
Lymphoproliferative Disorder
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Precancerous/Nonmalignant Condition
Unspecified Adult Solid Tumor, Protocol Specific
Drug: sunitinib malate
Other: liquid chromatography
Other: mass spectrometry
Other: pharmacological study
Phase I

Genetics Home Reference related topics: aceruloplasminemia hemophilia
MedlinePlus related topics: AIDS AIDS Medicines Cancer Fungal Infections Hodgkin's Disease Kidney Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma Multiple Myeloma
Drug Information available for: Sunitinib malate Sunitinib Malic acid
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: A Phase 1/Pharmacokinetic Study of Sunitinib in Patients With Cancer Who Also Have HIV and Are on HAART Therapy

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Safety [ Designated as safety issue: Yes ]
  • Pharmacological interactions [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Efficacy [ Designated as safety issue: No ]
  • Alterations in antiretroviral drug pharmacokinetics due to sunitinib malate [ Designated as safety issue: No ]
  • Alterations in immune parameters, including total leukocyte count, CD4 count, and viral load, during treatment with sunitinib malate [ Designated as safety issue: No ]
  • Correlation of variations in genes involved in sunitinib malate absorption, metabolism, and elimination (e.g., CYP3A4, CYP3A5, ABCB1, and ABCG2) with drug pharmacokinetics [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: May 2009
Estimated Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To determine the safety of sunitinib malate in HIV-positive patients with cancer undergoing highly active antiretroviral therapy (HAART) containing protease inhibitors and/or non-nucleoside reverse transcriptase inhibitors.
  • To investigate the pharmacological interactions of sunitinib malate.

Secondary

  • To evaluate the efficacy of sunitinib malate in treating patients with non-AIDS-defining cancers.
  • To detect alterations in antiretroviral drug pharmacokinetics due to sunitinib malate.
  • To detect alterations in immune parameters, including total leukocyte count, CD4 count, and viral load, during treatment with sunitinib malate.
  • To correlate variations in genes involved in sunitinib malate absorption, metabolism, and elimination (e.g., CYP3A4, CYP3A5, ABCB1, and ABCG2) with drug pharmacokinetics.

OUTLINE: This is a multicenter study. Patients are stratified according to type of highly active antiretroviral therapy (non-nucleoside reverse transcriptase inhibitor-based therapy vs non-ritonavir protease inhibitor [PI]-based therapy vs ritonavir PI-based therapy).

Patients receive oral sunitinib malate once daily for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for pharmacokinetic studies by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

After completion of study therapy, patients are followed for at least 1 month.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Biopsy proven malignancy, including any of the following:

    • Metastatic renal cell carcinoma
    • Other solid tumor malignancy, including non-AIDS-defining or AIDS-defining malignancy, that has progressed after standard therapy and/or for which other curative options are not available
    • Hematologic malignancy for which effective standard therapy or other curative options are not available

      • No blast phase leukemia
  • Serologic documentation of HIV infection by ELISA, western blot, or other federally approved licensed HIV test
  • CD4 count > 50 cells/µL
  • Has been on stable antiretroviral therapy for ≥ 4 weeks that includes a protease inhibitor-based or non-nucleoside reverse transcriptase inhibitor-based regimen of ≥ 3 drugs

    • Not planning to change the regimen within 8 weeks after starting study drug

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 70-100%
  • Life expectancy ≥ 3 months
  • Hemoglobin ≥ 8.0 g/dL
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Creatinine normal OR glomerular filtration rate > 60 mL/min
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (total bilirubin ≤ 3.5 mg/dL allowed if elevation is secondary to indinavir therapy AND direct bilirubin normal; if the elevation is secondary to atazanavir therapy, then there is no limit on the total bilirubin if the direct bilirubin is normal)
  • AST and ALT ≤ 2.5 times ULN
  • LVEF normal
  • QTc interval ≤ 500 msec
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for up to 3 months after completion of study treatment
  • No concurrent active opportunistic infection
  • No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
  • No active peptic ulcer disease
  • No clinically significant cardiovascular disease, including uncontrolled hypertension (i.e., diastolic blood pressure ≥ 100 mm Hg despite optimal medical therapy) or unstable angina
  • No myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, transient ischemic attack, or pulmonary embolism within the past 6 months
  • No ongoing ventricular cardiac dysrhythmias ≥ NCI CTCAE grade 2
  • No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
  • No serious cardiac arrhythmia requiring medication
  • No psychiatric illness that would limit compliance with study requirements
  • No pre-existing thyroid abnormality that cannot be maintained with medication to keep thyroid-stimulating hormone levels within the normal range
  • No other severe and/or life-threatening medical disease

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from prior therapy
  • No prior sunitinib malate
  • No prior surgical procedures affecting absorption
  • More than 14 days since prior treatment for an acute infection or other serious medical illness
  • More than 2 weeks since prior antineoplastic therapy, including investigational drugs or standard therapy
  • More than 3 weeks since prior major surgery or radiotherapy
  • No concurrent known CYP3A4 inhibitors or inducers (including grapefruit juice or star fruit) other than antiretroviral drugs used to treat HIV infection
  • No concurrent agents with proarrhythmic potential (e.g., terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, or flecainide)
  • No other concurrent therapies for the primary malignancy, including chemotherapy or biologic therapy
  • No other concurrent investigational drugs other than antiretroviral agents obtained through an expanded access protocol
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00890747

Sponsors and Collaborators
AIDS Associated Malignancies Clinical Trials Consortium
Investigators
Principal Investigator: John F. Deeken, MD Lombardi Cancer Research Center
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000639703, AMC-061
Study First Received: April 29, 2009
Last Updated: April 29, 2009
ClinicalTrials.gov Identifier: NCT00890747     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
HIV infection
stage IV renal cell cancer
recurrent renal cell cancer
unspecified adult solid tumor, protocol specific
accelerated phase chronic myelogenous leukemia
acute undifferentiated leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
atypical chronic myeloid leukemia
chronic myelomonocytic leukemia
chronic phase chronic myelogenous leukemia
mast cell leukemia
meningeal chronic myelogenous leukemia
progressive hairy cell leukemia, initial treatment
prolymphocytic leukemia
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
recurrent adult T-cell leukemia/lymphoma
refractory chronic lymphocytic leukemia
refractory hairy cell leukemia
relapsing chronic myelogenous leukemia
secondary acute myeloid leukemia
stage III adult T-cell leukemia/lymphoma
stage III chronic lymphocytic leukemia
stage IV adult T-cell leukemia/lymphoma
stage IV chronic lymphocytic leukemia
T-cell large granular lymphocyte leukemia

Study placed in the following topic categories:
Urogenital Neoplasms
Mantle Cell Lymphoma
Preleukemia
Leukemia, Prolymphocytic
Hemorrhagic Disorders
Lymphoma, Large-Cell, Anaplastic
Neoplasm Metastasis
Thrombocythemia, Hemorrhagic
Kidney Diseases
Myelodysplastic Myeloproliferative Disease
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Blood Coagulation Disorders
Leukemia, Myeloid
Carcinoma
Waldenstrom Macroglobulinemia
Plasmacytoma
Leukemia, Myeloid, Accelerated Phase
HIV Infections
Chronic Myelogenous Leukemia
Lymphoma, Non-Hodgkin
Neoplasms, Glandular and Epithelial
Precancerous Conditions
Blood Protein Disorders
Lymphoma, Follicular
Sezary Syndrome
Lymphoblastic Lymphoma
Lymphoma, B-Cell

Additional relevant MeSH terms:
Precancerous Conditions
Antineoplastic Agents
Blood Protein Disorders
Physiological Effects of Drugs
Paraproteinemias
Urogenital Neoplasms
Hemostatic Disorders
Urologic Neoplasms
Leukemia
Preleukemia
Hemorrhagic Disorders
Pathologic Processes
Neoplasms by Site
Urologic Diseases
Sunitinib
Kidney Neoplasms
Therapeutic Uses
Syndrome
Lymphoma, Large-Cell, Immunoblastic
Cardiovascular Diseases
Growth Inhibitors
Angiogenesis Modulating Agents
Kidney Diseases
Lymphoma
Immunoproliferative Disorders
Disease
Neoplasms by Histologic Type
Immune System Diseases
Hematologic Diseases
Growth Substances

ClinicalTrials.gov processed this record on May 07, 2009