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Accelerated Phase Chronic Myelogenous LeukemiaPhase 1NCT00890747

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

A Phase 1 study testing sunitinib malate, pharmacological study and laboratory biomarker analysis in people with Accelerated Phase Chronic Myelogenous Leukemia and Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, run by National Cancer Institute (NCI) at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
sunitinib malate, pharmacological study and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
11 sitesUnited States
Study dates
Aug 2009to May 2011
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Northwestern University

    Chicago, Illinois, 60611

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Abramson Cancer Center of The University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • AIDS - Associated Malignancies Clinical Trials Consortium

    Rockville, Maryland, 20850

  • Washington University - Jewish

    Saint Loius, Missouri, 63110

  • Virginia Mason Medical Center

    Seattle, Washington, 98101

  • Albert Einstein College of Medicine

    The Bronx, New York, 10461

  • Lombardi Comprehensive Cancer Center at Georgetown University

    Washington D.C., District of Columbia, 20057

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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.

Being tested
sunitinib malate, pharmacological study, laboratory biomarker analysis
Keywords
HIV Infections, treatment experienced
Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Leukemia, Biphenotypic, Acute, Congenital Abnormalities, Histiocytosis, Langerhans-Cell, Lymphoma, Extranodal NK-T-Cell, Leukemia, Large Granular Lymphocytic, Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • sunitinib malateDrug

    Also called SU11248, sunitinib, Sutent

    Given PO

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00890747
Study groupRoleWhat they receive
Treatment (sunitinib malate)ExperimentalPatients receive sunitinib malate PO daily on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Drug: sunitinib malate; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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]).

    Measured: Up to 30 days after completion of study treatment

  2. 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

    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]).

    Measured: 6 weeks

Secondary outcomes (3)

  1. Evaluation of response

    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.

    Measured: Up to 30 days after completion of study treatment

  2. Antiretroviral drug pharmacokinetics due to sunitinib malate

    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.

    Measured: At baseline and at 1, 2, 3, 4, 5, 6, 7, 8, and 24 hours of days 1and 2

  3. Alterations in immune parameters, including total leukocyte count, CD4, and viral load

    Measured: Up to 30 days after completion of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Apr 2009 (estimated)
  2. Study startAug 2009
  3. Primary completionMay 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00890747
Sponsor's protocol ID
NCI-2012-02208
Other IDs
NCI-2012-02208, AMC-061, AMC-061, U01CA121947
Status last verified
Sep 2013
First submitted
29 Apr 2009
Last updated
17 Mar 2014
Results posted
No

Publications

  • Rudek MA, Moore PC, Mitsuyasu RT, Dezube BJ, Aboulafia D, Gerecitano J, Sullivan R, Cianfrocca ME, Henry DH, Ratner L, Haigentz M Jr, Dowlati A, Little RF, Ivy SP, Deeken JF. A phase 1/pharmacokinetic study of sunitinib in combination with highly active antiretroviral therapy in human immunodeficiency virus-positive patients with cancer: AIDS Malignancy Consortium trial AMC 061. Cancer. 2014 Apr 15;120(8):1194-202. doi: 10.1002/cncr.28554. Epub 2014 Jan 28.

    PubMed 24474568

  • Rais R, Zhao M, He P, Xu L, Deeken JF, Rudek MA. Quantitation of unbound sunitinib and its metabolite N-desethyl sunitinib (SU12662) in human plasma by equilibrium dialysis and liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study. Biomed Chromatogr. 2012 Nov;26(11):1315-24. doi: 10.1002/bmc.2697. Epub 2012 Jan 18.

    PubMed 22259028

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing sunitinib malate, pharmacological study and laboratory biomarker analysis in people with Accelerated Phase Chronic Myelogenous Leukemia and Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, run by National Cancer Institute (NCI) at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00890747, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2014.

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