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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
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

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

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]).

Outcome Time Frame:

Up to 30 days after completion of study treatment

Safety Issue:

Yes

Principal Investigator

John Deeken

Investigator Role:

Principal Investigator

Investigator Affiliation:

AIDS Associated Malignancies Clinical Trials Consortium

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02208

NCT ID:

NCT00890747

Start Date:

August 2009

Completion Date:

Related Keywords:

  • 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
  • HIV Infections
  • treatment experienced
  • Congenital Abnormalities
  • Acquired Immunodeficiency Syndrome
  • HIV Infections
  • Aggression
  • Primary Myelofibrosis
  • Amyloidosis
  • Burkitt Lymphoma
  • Neoplasms
  • Carcinoma
  • Carcinoma, Renal Cell
  • Histiocytosis
  • Histiocytosis, Langerhans-Cell
  • Hodgkin Disease
  • Immunoblastic Lymphadenopathy
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Hairy Cell
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Mast-Cell
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myeloid, Accelerated Phase
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid, Chronic-Phase
  • Leukemia, Myelomonocytic, Chronic
  • Leukemia, Neutrophilic, Chronic
  • Leukemia, Prolymphocytic
  • Leukemia, T-Cell
  • Leukemia-Lymphoma, Adult T-Cell
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphomatoid Granulomatosis
  • Lymphoproliferative Disorders
  • Waldenstrom Macroglobulinemia
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Mycoses
  • Mycosis Fungoides
  • Myelodysplastic Syndromes
  • Preleukemia
  • Leukemia, Myelomonocytic, Acute
  • Myeloproliferative Disorders
  • Polycythemia
  • Polycythemia Vera
  • Sezary Syndrome
  • Thrombocythemia, Essential
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Cutaneous
  • Lymphoma, T-Cell, Peripheral
  • Hypereosinophilic Syndrome
  • Lymphoma, Large-Cell, Anaplastic
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Extranodal NK-T-Cell
  • Lymphoma, Mantle-Cell
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
  • Thrombocytosis
  • Myelodysplastic-Myeloproliferative Diseases
  • Leukemia, Large Granular Lymphocytic

Name

Location
Albert Einstein College of Medicine Bronx, New York  10461
Memorial Sloan Kettering Cancer Center New York, New York  10021
Beth Israel Deaconess Medical Center Boston, Massachusetts  02215
Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania  19104-4283
Virginia Mason Medical Center Seattle, Washington  98111
Northwestern University Chicago, Illinois  60611
Case Western Reserve University Cleveland, Ohio  44106
Lombardi Comprehensive Cancer Center at Georgetown University Washington, District of Columbia  20057
Jonsson Comprehensive Cancer Center Los Angeles, California  90095
AIDS - Associated Malignancies Clinical Trials Consortium Rockville, Maryland  20850
Washington University - Jewish Saint Loius, Missouri  63110