A Phase 1/Pharmacokinetic Study of Sunitinib in Patients With Cancer Who Also Have HIV and Are on HAART Therapy
Overview
- Phase
- Phase 1
- Intervention
- sunitinib malate
- Conditions
- Accelerated Phase Chronic Myelogenous Leukemia
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 42
- Locations
- 11
- Primary Endpoint
- Grades 3, 4, and 5, treatment-related adverse events, graded according to the National Cancer Institute (NCI) CTCAE version 3.0
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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.
Investigators
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
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
Arms & Interventions
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.
Intervention: sunitinib malate
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.
Intervention: pharmacological study
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.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
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 \[CV\]).
Secondary Outcomes
- Evaluation of response(Up to 30 days after completion of study treatment)
- Antiretroviral drug pharmacokinetics due to sunitinib malate(At baseline and at 1, 2, 3, 4, 5, 6, 7, 8, and 24 hours of days 1and 2)
- Alterations in immune parameters, including total leukocyte count, CD4, and viral load(Up to 30 days after completion of study treatment)