Sunitinib Malate in Treating East African Patients With Kaposi Sarcoma

This study has been withdrawn prior to enrollment.
(No participants enrolled.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00521092
First received: August 24, 2007
Last updated: May 2, 2014
Last verified: December 2012
  Purpose

Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. This phase II trial is studying the side effects and how well sunitinib malate works in treating patients with Kaposi sarcoma.


Condition Intervention Phase
AIDS-related Kaposi Sarcoma
Classic Kaposi Sarcoma
Drug: sunitinib malate
Procedure: laboratory biomarker analysis
Procedure: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Sunitinib (SU11248) in Patients With Kaposi's Sarcoma in East Africa

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Response rate [ Time Frame: Up to 11 months ] [ Designated as safety issue: No ]
    The true response rate will be estimated based on the number of responses using a binomial distribution. The confidence intervals for them can be estimated using same distribution. Chi-square test or Fisher's exact test will be used to examine the difference of response rate between the two cohorts and log-rank test for the difference of survival outcomes.

  • Overall survival [ Time Frame: From the date of treatment to date of death, assessed up to 11 months ] [ Designated as safety issue: No ]
    Will be estimated by Kaplan-Meier method.

  • Progression-free survival [ Time Frame: From the date of treatment to date of death or date of disease progression, assessed up to 11 months ] [ Designated as safety issue: No ]
    Will be estimated by Kaplan-Meier method.

  • Levels of plasma-associated HIV-1 RNA viral load and cell-associated KSHV DNA viral load [ Time Frame: Up to 11 months ] [ Designated as safety issue: No ]
    Multivariate analysis will be performed using the Cox proportional hazards model. The effects of CD4+ lymphocyte counts, plasma HIV-1 RNA viral load and KSHV DNA level on the objective response rate will be evaluated using multivariate logistic regression.


Secondary Outcome Measures:
  • Changes in CD4+ and CD8+ cell counts, levels of plasma-associated HIV-1 RNA, and cell-associated KSHV DNA load [ Time Frame: Baseline and 6 weeks ] [ Designated as safety issue: No ]
    For each treatment cohort and for all groups combined, the Wilcoxon signed rank test (the non-parametric version of paired T-test) will be used to evaluate the changes.


Enrollment: 0
Study Start Date: January 2009
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral sunitinib malate 50 mg once daily for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Drug: sunitinib malate
Given orally
Other Names:
  • SU11248
  • sunitinib
  • Sutent
Procedure: laboratory biomarker analysis
Correlative study
Procedure: pharmacological study
Correlative study
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the clinical response of sunitinib malate in patients with Kaposi sarcoma (KS) in Uganda and Kenya.

II. Compare clinical response rates in endemic versus epidemic (AIDS) KS. III. Determine the safety and tolerability of sunitinib malate in patients with endemic or epidemic (AIDS) KS.

SECONDARY OBJECTIVES:

I Monitor the impact of sunitinib malate on underlying HIV-1 and Kaposi sarcoma-associated herpesvirus (KSHV) viral infection (HIV-1 plasma RNA and KSHV cell-associated DNA).

II. Evaluate morphological changes in KS lesions after treatment. III. Determine the pharmacokinetic profile of sunitinib malate in patients with KS.

IV Evaluate KSHV gene expression in endemic and epidemic KS lesions in patients in Uganda and Kenya.

OUTLINE: This is a multicenter study. Patients are stratified according to HIV-serostatus (endemic [HIV-seronegative] vs epidemic [HIV-seropositive/AIDS] kaposi sarcoma).

Patients receive oral sunitinib malate 50 mg once daily for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor tissue and blood sample collection periodically for correlative and pharmacokinetic studies. Samples are analyzed for CD4 lymphocyte counts, HIV-1 plasma RNA levels, KSHV specific antibodies, expression pattern of KSHV in vitro and in vivo, expression of latently versus lytically expressed genes in tumor tissue, and plasma concentrations of sunitinib malate and its active metabolite, SU12662.

After completion of study treatment, patients are followed every 6 weeks.

  Eligibility

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

Inclusion Criteria:

  • ECOG performance status 0-1
  • Documented HIV-serostatus [HIV-seronegative (endemic KS) or HIV-seropositive (epidemic/AIDS KS)]
  • No symptomatic organ involvement, visceral crisis, or life-threatening disease (e.g., extensive or symptomatic pulmonary disease or reticuloendothelial system/hepatic involvement) for which aggressive double- or triple-drug combination chemotherapy for urgent cytoreduction is indicated (i.e., doxorubicin hydrochloride, bleomycin, and vinblastine [ABV], BV, or AV)
  • Histologically confirmed Kaposi sarcoma
  • Platelet count > 75,000/uL
  • Life expectancy >= 24 weeks
  • Absolute granulocyte count > 1,000/uL
  • Hemoglobin > 8.0 g/dL OR hematocrit > 24%
  • Serum creatinine =< 2.0 mg/dL
  • AST < 3 times normal
  • Fertile patients must use effective contraception
  • Normal clinical cardiac examination and normotensive (systolic and diastolic BP < 140/90 mm Hg) documented on at least two occasions prior to enrollment
  • Normal ECG including QTc interval < 500 msec
  • Normal echocardiogram prior to enrollment (if feasibly possible)
  • Must be able to swallow study medication
  • No acute infections [Patients with chronic infections (e.g., malaria, tuberculosis, parasitic infections, or hepatitis B or C) that may be active but under treatment are allowed provided all eligibility criteria are met]
  • At least 60 days since prior local treatment modalities (e.g., resection, cryosurgery, radiotherapy, or intralesional therapy) AND treated lesions must have clearly progressed following such therapies if the lesions are to be used as an index lesion
  • No prior systemic anticancer therapy for Kaposi sarcoma
  • Concurrent antiretroviral therapy required for HIV-seropositive patients (Patient must be on a stable regimen 8 weeks prior to study enrollment--An exception may be made for patients who have exhausted or are intolerant to all available regimens)
  • No other concurrent systemic anticancer therapy
  • Patient resides in Uganda or Kenya, East Africa

Exclusion Criteria:

  • Pregnant or nursing
  • Baseline diarrhea >= grade 2 by CTCAE
  • Uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Ongoing or acute active infection
    • Symptomatic congestive heart failure (NYHA class III or IV heart disease)
    • Unstable angina pectoris
  • Uncontrolled intercurrent illness including, but not limited to, any of the following: 1) Cardiac arrhythmia (i.e., history of serious ventricular arrhythmia, ventricular fibrillation, or ventricular tachycardia >= 3 beats in a row OR QTc >= 500 msec) 2) Psychiatric illness or social situation that would limit compliance with study requirements
  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: NCT00521092

Sponsors and Collaborators
Investigators
Principal Investigator: Scot Remick Case Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00521092     History of Changes
Other Study ID Numbers: NCI-2009-00229, NCI-2009-00229, CASE 1706 - AMC 049, CDR0000561751, CASE 1706 / AMC 049, 7831, U01CA062502, P30AI036219
Study First Received: August 24, 2007
Last Updated: May 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
Treatment Experienced

Additional relevant MeSH terms:
Sarcoma, Kaposi
AIDS-Related Opportunistic Infections
Sarcoma
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Vascular Tissue
Opportunistic Infections
Infection
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Parasitic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014