Sunitinib Malate in Treating HIV-Positive Patients With Cancer Receiving Antiretroviral Therapy
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ClinicalTrials.gov Identifier: NCT00890747 |
Recruitment Status
:
Completed
First Posted
: April 30, 2009
Last Update Posted
: March 17, 2014
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Condition or disease | Intervention/treatment | Phase |
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Accelerated Phase Chronic Myelogenous Leukemia Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome Acute Undifferentiated Leukemia Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) 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) Adult Grade III Lymphomatoid Granulomatosis Adult Langerhans Cell Histiocytosis Adult Nasal Type Extranodal NK/T-cell Lymphoma Aggressive NK-cell Leukemia AIDS-related Diffuse Large Cell Lymphoma AIDS-related Diffuse Mixed Cell Lymphoma AIDS-related Diffuse Small Cleaved Cell Lymphoma AIDS-related Immunoblastic Large Cell Lymphoma AIDS-related Lymphoblastic Lymphoma AIDS-related Malignancies AIDS-related Small Noncleaved Cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative Chronic Eosinophilic Leukemia Chronic Myelomonocytic Leukemia Chronic Neutrophilic Leukemia Chronic Phase Chronic Myelogenous Leukemia Clear Cell Renal Cell Carcinoma Cutaneous B-cell Non-Hodgkin Lymphoma de Novo Myelodysplastic Syndromes Essential Thrombocythemia Extramedullary Plasmacytoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Hepatosplenic T-cell Lymphoma HIV Infection HIV-associated Hodgkin Lymphoma Intraocular Lymphoma Isolated Plasmacytoma of Bone Light Chain Deposition Disease Mast Cell Leukemia Myelodysplastic Syndrome With Isolated Del(5q) Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Myeloid/NK-cell Acute Leukemia Nodal Marginal Zone B-cell Lymphoma Noncutaneous Extranodal Lymphoma Osteolytic Lesions of Multiple Myeloma Peripheral T-cell Lymphoma Plasma Cell Neoplasm Polycythemia Vera Post-transplant Lymphoproliferative Disorder Previously Treated Myelodysplastic Syndromes Primary Myelofibrosis Primary Systemic Amyloidosis Progressive Hairy Cell Leukemia, Initial Treatment Prolymphocytic Leukemia Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Grade III Lymphomatoid Granulomatosis Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Renal Cell Cancer Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Hairy Cell Leukemia Refractory Multiple Myeloma Relapsing Chronic Myelogenous Leukemia Stage IV Renal Cell Cancer T-cell Large Granular Lymphocyte Leukemia Testicular Lymphoma Unspecified Adult Solid Tumor, Protocol Specific Waldenström Macroglobulinemia | Drug: sunitinib malate Other: pharmacological study Other: laboratory biomarker analysis | Phase 1 |
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 (Clinical Trial) |
Actual Enrollment : | 42 participants |
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 : | August 2009 |
Actual Primary Completion Date : | May 2011 |

Arm | Intervention/treatment |
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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.
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Drug: sunitinib malate
Given PO
Other Names:
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
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- 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]).
- 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 ]

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Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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
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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
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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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00890747
United States, California | |
Jonsson Comprehensive Cancer Center | |
Los Angeles, California, United States, 90095 | |
United States, District of Columbia | |
Lombardi Comprehensive Cancer Center at Georgetown University | |
Washington, District of Columbia, United States, 20057 | |
United States, Illinois | |
Northwestern University | |
Chicago, Illinois, United States, 60611 | |
United States, Maryland | |
AIDS - Associated Malignancies Clinical Trials Consortium | |
Rockville, Maryland, United States, 20850 | |
United States, Massachusetts | |
Beth Israel Deaconess Medical Center | |
Boston, Massachusetts, United States, 02215 | |
United States, Missouri | |
Washington University - Jewish | |
Saint Loius, Missouri, United States, 63110 | |
United States, New York | |
Albert Einstein College of Medicine | |
Bronx, New York, United States, 10461 | |
Memorial Sloan Kettering Cancer Center | |
New York, New York, United States, 10065 | |
United States, Ohio | |
Case Western Reserve University | |
Cleveland, Ohio, United States, 44106 | |
United States, Pennsylvania | |
Abramson Cancer Center of The University of Pennsylvania | |
Philadelphia, Pennsylvania, United States, 19104 | |
United States, Washington | |
Virginia Mason Medical Center | |
Seattle, Washington, United States, 98101 |
Principal Investigator: | John Deeken | AIDS Associated Malignancies Clinical Trials Consortium |
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00890747 History of Changes |
Obsolete Identifiers: | NCT01727102 |
Other Study ID Numbers: |
NCI-2012-02208 NCI-2012-02208 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) AMC-061 ( Other Identifier: AIDS - Associated Malignancies Clinical Trials Consortium ) AMC-061 ( Other Identifier: CTEP ) U01CA121947 ( U.S. NIH Grant/Contract ) |
First Posted: | April 30, 2009 Key Record Dates |
Last Update Posted: | March 17, 2014 |
Last Verified: | September 2013 |
Keywords provided by National Cancer Institute (NCI):
HIV Infections treatment experienced |
Additional relevant MeSH terms:
Lymphoma Syndrome Leukemia Neoplasms Leukemia, Myeloid Multiple Myeloma Neoplasms, Plasma Cell Leukemia, Myeloid, Acute Lymphoma, Follicular HIV Infections Myelodysplastic Syndromes Preleukemia Lymphoma, Non-Hodgkin Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma |
Leukemia, Lymphocytic, Chronic, B-Cell Lymphoma, B-Cell Hodgkin Disease Lymphoma, Mantle-Cell Leukemia, Myelogenous, Chronic, BCR-ABL Positive Lymphoma, B-Cell, Marginal Zone Carcinoma, Renal Cell Lymphoma, Large B-Cell, Diffuse Burkitt Lymphoma Lymphoma, T-Cell Lymphoma, Large-Cell, Immunoblastic Plasmablastic Lymphoma Mycoses Primary Myelofibrosis Mycosis Fungoides |