Clinical trial NCT00521092: Sunitinib Malate in Treating East African Patients With Kaposi Sarcoma
Official title: Phase II Study of Sunitinib (SU11248) in Patients With Kaposi's Sarcoma in East Africa
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: AIDS-related Kaposi Sarcoma
Classic Kaposi Sarcoma
Keywords: Treatment Experienced
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2007-08-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Response rate
timeFrame: Up to 11 months
measure: Overall survival
timeFrame: From the date of treatment to date of death, assessed up to 11 months
measure: Progression-free survival
timeFrame: From the date of treatment to date of death or date of disease progression, assessed up to 11 months
measure: Levels of plasma-associated HIV-1 RNA viral load and cell-associated KSHV DNA viral load
timeFrame: Up to 11 months
Secondary outcomes:
measure: Changes in CD4+ and CD8+ cell counts, levels of plasma-associated HIV-1 RNA, and cell-associated KSHV DNA load
timeFrame: Baseline and 6 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Case Comprehensive Cancer Center
name: Scot Remick
role: PRINCIPAL_INVESTIGATOR
References: