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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00890747
First received: April 29, 2009
Last updated: March 14, 2014
Last verified: September 2013
  Purpose

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 Intervention Phase
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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Acute Myelocytic Leukemia Acute Myeloid Leukemia, Adult Acute Non Lymphoblastic Leukemia Aggressive NK Cell Leukemia AL Amyloidosis Anaplastic Large Cell Lymphoma Anaplastic Plasmacytoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Angioimmunoblastic T-cell Lymphoma B-cell Lymphomas Burkitt Lymphoma Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Chronic Myelomonocytic Leukemia Chronic Myeloproliferative Disorders Chronic Neutrophilic Leukemia Clear Cell Renal Cell Carcinoma Cutaneous T-cell Lymphoma Essential Thrombocythemia Follicular Lymphoma Hairy Cell Leukemia Hand-Schuller-Christian Disease Hodgkin Lymphoma Hypereosinophilic Syndrome Kidney Cancer Langerhans Cell Histiocytosis Large Granular Lymphocyte Leukemia Leukemia, B-cell, Chronic Leukemia, Myeloid Leukemia, T-cell, Chronic Light Chain Deposition Disease Lymphoblastic Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Lymphoma, Small Cleaved-cell, Diffuse Lymphomatoid Granulomatosis Lymphosarcoma Mantle Cell Lymphoma Mastocytosis Multiple Myeloma Mycosis Fungoides Myelodysplastic Syndromes Myelodysplastic/myeloproliferative Disease Myelofibrosis Peripheral T-cell Lymphoma Plasmablastic Lymphoma Polycythemia Vera Renal Cancer Sezary Syndrome Small Non-cleaved Cell Lymphoma Systemic Mastocytosis Waldenstrom Macroglobulinemia
U.S. FDA Resources

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

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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:
  • Evaluation of response [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

Enrollment: 42
Study Start Date: August 2009
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00890747

Locations
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
Sponsors and Collaborators
Investigators
Principal Investigator: John Deeken AIDS Associated Malignancies Clinical Trials Consortium
  More Information

Publications:
Additional 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, AMC-061, AMC-061, U01CA121947
Study First Received: April 29, 2009
Last Updated: March 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
HIV Infections
treatment experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Amyloidosis
Burkitt Lymphoma
Carcinoma, Renal Cell
Histiocytosis
Histiocytosis, Langerhans-Cell
Hodgkin Disease
Hypereosinophilic Syndrome
Immunoblastic Lymphadenopathy
Infection
Intraocular Lymphoma
Leukemia
Leukemia, Hairy Cell
Leukemia, Large Granular Lymphocytic
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Mast-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myeloid, Acute
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Neutrophilic, Chronic
Leukemia, Prolymphocytic
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell

ClinicalTrials.gov processed this record on October 23, 2014