Brief Title
Sunitinib Malate in Treating HIV-Positive Patients With Cancer Receiving Antiretroviral Therapy
Official Title
A Phase 1/Pharmacokinetic Study of Sunitinib in Patients With Cancer Who Also Have HIV and Are on HAART Therapy
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.
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Grades 3, 4, and 5, treatment-related adverse events, graded according to the National Cancer Institute (NCI) CTCAE version 3.0
Secondary Outcome
Evaluation of response
Condition
Accelerated Phase Chronic Myelogenous Leukemia
Intervention
sunitinib malate
Study Arms / Comparison Groups
Treatment (sunitinib malate)
Description: Patients receive sunitinib malate PO daily on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
42
Start Date
August 2009
Primary Completion Date
May 2011
Eligibility 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
John Deeken, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00890747
Organization ID
NCI-2012-02208
Secondary IDs
NCI-2012-02208
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
John Deeken, Principal Investigator, AIDS Associated Malignancies Clinical Trials Consortium
Verification Date
September 2013