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Sunitinib Malate in Treating East African Patients With Kaposi Sarcoma

Primary Purpose

AIDS-related Kaposi Sarcoma, Classic Kaposi Sarcoma

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

sunitinib malate

laboratory biomarker analysis

pharmacological study

About this trial

This is an interventional treatment trial for AIDS-related Kaposi Sarcoma focused on measuring Treatment Experienced

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

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.

Outcomes

Primary Outcome Measures

Response rate

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

Will be estimated by Kaplan-Meier method.

Progression-free survival

Will be estimated by Kaplan-Meier method.

Levels of plasma-associated HIV-1 RNA viral load and cell-associated KSHV DNA viral load

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

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.

Full Information

NCT ID

NCT00521092

First Posted

August 24, 2007

Last Updated

May 2, 2014

Sponsor

National Cancer Institute (NCI)

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

1. Study Identification

Unique Protocol Identification Number

NCT00521092

Brief Title

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

2. Study Status

Record Verification Date

December 2012

Overall Recruitment Status

Withdrawn

Why Stopped

No participants enrolled.

Study Start Date

January 2009 (undefined)

Primary Completion Date

October 2010 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Cancer Institute (NCI)

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

AIDS-related Kaposi Sarcoma, Classic Kaposi Sarcoma

Keywords

Treatment Experienced

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

sunitinib malate

Other Intervention Name(s)

SU11248, sunitinib, Sutent

Intervention Description

Given orally

Intervention Type

Procedure

Intervention Name(s)

laboratory biomarker analysis

Intervention Description

Correlative study

Intervention Type

Procedure

Intervention Name(s)

pharmacological study

Other Intervention Name(s)

pharmacological studies

Intervention Description

Correlative study

Primary Outcome Measure Information:

Title

Response rate

Description

Time Frame

Up to 11 months

Title

Overall survival

Description

Will be estimated by Kaplan-Meier method.

Time Frame

From the date of treatment to date of death, assessed up to 11 months

Title

Progression-free survival

Description

Will be estimated by Kaplan-Meier method.

Time Frame

From the date of treatment to date of death or date of disease progression, assessed up to 11 months

Title

Levels of plasma-associated HIV-1 RNA viral load and cell-associated KSHV DNA viral load

Description

Time Frame

Up to 11 months

Secondary Outcome Measure Information:

Title

Changes in CD4+ and CD8+ cell counts, levels of plasma-associated HIV-1 RNA, and cell-associated KSHV DNA load

Description

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.

Time Frame

Baseline and 6 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Scot Remick

Organizational Affiliation

Case Comprehensive Cancer Center

Official's Role

Principal Investigator

12. IPD Sharing Statement

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Sunitinib Malate in Treating East African Patients With Kaposi Sarcoma

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