Sunitinib Malate in Treating East African Patients With Kaposi Sarcoma
Maneno muhimu
Kikemikali
Maelezo
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.
Tarehe
| Imethibitishwa Mwisho: | 11/30/2012 |
| Iliyowasilishwa Kwanza: | 08/23/2007 |
| Uandikishaji uliokadiriwa Uliwasilishwa: | 08/23/2007 |
| Iliyotumwa Kwanza: | 08/26/2007 |
| Sasisho la Mwisho Liliwasilishwa: | 05/01/2014 |
| Sasisho la Mwisho Lilichapishwa: | 05/04/2014 |
| Tarehe halisi ya kuanza kwa masomo: | 12/31/2008 |
| Tarehe ya Kukamilisha Msingi iliyokadiriwa: | 09/30/2010 |
Hali au ugonjwa
Uingiliaji / matibabu
Drug: Arm I
Procedure: Arm I
Procedure: Arm I
Awamu
Vikundi vya Arm
| Mkono | Uingiliaji / matibabu |
|---|---|
| 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: Arm I Given orally |
Vigezo vya Kustahiki
| Zama zinazostahiki Kujifunza | 18 Years Kwa 18 Years |
| Jinsia Inastahiki Kujifunza | All |
| Hupokea Wajitolea wa Afya | Ndio |
| Vigezo | 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 |
Matokeo
Hatua za Matokeo ya Msingi
1. Response rate [Up to 11 months]
2. Overall survival [From the date of treatment to date of death, assessed up to 11 months]
3. Progression-free survival [From the date of treatment to date of death or date of disease progression, assessed up to 11 months]
4. Levels of plasma-associated HIV-1 RNA viral load and cell-associated KSHV DNA viral load [Up to 11 months]
Hatua za Matokeo ya Sekondari
1. Changes in CD4+ and CD8+ cell counts, levels of plasma-associated HIV-1 RNA, and cell-associated KSHV DNA load [Baseline and 6 weeks]
