Clinical trial NCT00075777: Valproic Acid in Treating Patients With Kaposi's Sarcoma
Official title: A Pilot Trial Of Valproic Acid In Patients With Kaposi's Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sarcoma
Keywords: recurrent Kaposi sarcoma
AIDS-related Kaposi sarcoma
Lead sponsor: AIDS Malignancy Consortium
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: The Emmes Company, LLC
First posted: 2004-01-13
Enrollment: 19
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: RATIONALE: Valproic acid may help stop the growth of Kaposi's sarcoma cells by blocking the enzymes necessary for tumor cell growth.

PURPOSE: This clinical trial is studying valproic acid in treating patients with HIV-related Kaposi's sarcoma.

Detailed description: OBJECTIVES:

Primary

* Determine the safety of valproic acid in patients with Kaposi's sarcoma.
* Determine the effects of this drug on human herpes virus 8 (KSHV) gene expression using polymerase chain reaction and immunohistochemistry in these patients.

Secondary

* Determine the effects of this drug on HIV, KSHV, and Epstein-Barr virus viral loads in the plasma and peripheral blood mononuclear cells of these patients.
* Determine clinical response in patients treated with this drug.

OUTLINE: This is an open-label, pilot, multicenter study.

Patients receive oral valproic acid twice daily on days 1-28 followed by a drug taper over 2 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly for 6 months.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 1 year.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed HIV-related Kaposi's sarcoma (KS)

  * Disease involving the skin and/or lymph nodes

    * No symptomatic visceral disease
    * No oral KS as the only site of disease
  * Slowly progressive or stable disease allowed

    * Slow progression defined as fewer than 5 new lesions per month
  * Must have documented HIV infection by positive ELISA, western Blot, or viral load determination
* CD4 T-cell count \> 50/mm\^3

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Karnofsky 60-100%

Life expectancy

* At least 3 months

Hematopoietic

* Hemoglobin ≥ 8.0 g/dL
* Absolute neutrophil count ≥ 750/mm\^3
* Platelet count ≥ 75,000/mm\^3

Hepatic

* Bilirubin ≤ 1.5 times upper limit of normal (ULN)\*
* AST and ALT ≤ 3 times ULN
* Albumin \> 2.5 g/dL NOTE: \*Elevated total bilirubin (≤ 3.5 mg/dL) secondary to indinavir therapy allowed provided the direct bilirubin is normal

Renal

* Creatinine \< 1.5 times ULN

Cardiovascular

* No prior myocardial infarction
* No evidence of cardiac ischemia

Other

* Not pregnant
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 3 months after study participation
* No prior lactic acidosis \> 2.0 mmoles/L
* No prior lipoatrophy or hypercholesterolemia secondary to retroviral treatment
* No concurrent, acute, active opportunistic infection other than oral thrush or genital herpes within the past 14 days
* No other concurrent neoplasm requiring cytotoxic therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

* More than 2 weeks since prior biologic therapy for KS

Chemotherapy

* More than 2 weeks since prior chemotherapy for KS
* No concurrent systemic cytotoxic chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* More than 2 weeks since prior radiotherapy for KS

Surgery

* Not specified

Other

* More than 2 weeks since other prior antineoplastic or local therapy for KS
* More than 2 weeks since prior investigational therapy for KS
* More than 60 days since prior local therapy to a KS-marker lesion unless lesion has clearly progressed since therapy
* More than 1 year since prior valproic acid
* Concurrent antiretroviral therapy allowed provided regimen has been stable for at least 4 weeks
* No concurrent zidovudine
* No other concurrent KS-specific therapy
* No other concurrent investigational drugs, other than IND-approved antiretroviral agents

Primary outcomes:
measure: Toxicity-related discontinuation rate
timeFrame: 28 days
measure: Lytic induction rate
timeFrame: 28 days
measure: Clinical response rate
timeFrame: 28 days
measure: Accelerated KS progression rate
timeFrame: 28 days
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center at UCLA
state: California
city: San Diego
country: United States
facility: Veterans Affairs Medical Center - San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: Atlanta
country: United States
facility: Georgia Cancer Center for Excellence at Grady Memorial Hospital
state: Georgia
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital
state: Missouri
city: Bronx
country: United States
facility: Albert Einstein Cancer Center at Albert Einstein College of Medicine
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Joan Karnell Cancer Center at Pennsylvania Hospital
state: Pennsylvania
city: Seattle
country: United States
facility: Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center
state: Washington
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Richard F. Ambinder, MD, PhD
role: STUDY_CHAIR
affiliation: Georgia Cancer Center for Excellence at Grady Memorial Hospital
name: Mary Jo Lechowicz, MD
role: STUDY_CHAIR
References: