Liposomal Doxorubicin and Interleukin-12 in Treating Patients With AIDS-Related Kaposi's Sarcoma

Sarcoma Clinical Trial

Official title:

A Phase II Study of Liposomal Doxorubicin and Interleukin-12 in AIDS-Associated Kaposi's Sarcoma Followed by Chronic Administration of Interleukin-12

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00020449
• Other study ID #: CDR0000068502
• Secondary ID: NCI-01-C-0067NCI
• Status: Completed
• Phase: Phase 2
• First received: July 11, 2001
• Last updated: June 18, 2013
• Start date: January 2001
• Est. completion date: May 2004

Study information

• Verified date: March 2004
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill the tumor cells. Combining chemotherapy with interleukin-12 may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining liposomal doxorubicin with interleukin-12 in treating patients who have AIDS-related Kaposi's sarcoma.

Description:

OBJECTIVES:

• Determine the overall response rate in patients with AIDS-associated Kaposi's sarcoma (KS) treated with doxorubicin HCl liposome and interleukin-12.

• Determine the time to response and the number of complete responses in patients treated with this regimen.

• Determine the progression-free survival of patients treated with this regimen.

• Provide pilot information on the ability of interleukin-12 to maintain major responses induced with paclitaxel salvage therapy in patients with aggressive or life-threatening KS after treatment failure with doxorubicin HCl liposome and interleukin-12.

• Determine the effect of this regimen on CD4 counts and viral load in these patients.

OUTLINE: Patients receive doxorubicin HCl liposome (LipoDox) IV over 30 minutes once every 3 weeks for a total of 6 doses. Beginning concurrently with the initiation of LipoDox, patients also receive interleukin-12 (IL-12) subcutaneously twice weekly (at least 3 days apart) for up to 3 years.

Patients with refractory disease are transferred to the paclitaxel salvage therapy regimen comprising paclitaxel IV continuously on days 1-4 once every 3 weeks until a major response is achieved. Beginning concurrently with the initiation of paclitaxel salvage therapy, patients also receive IL-12 as above for up to 3 years.

Treatment continues in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response may discontinue IL-12 administration. If necessary, IL-12 treatment may resume at a later time.

Patients are followed at 4 weeks.

PROJECTED ACCRUAL: A total of 24-36 patients will be accrued for this study within 2-4 years.

Other known NCT identifiers

• NCT00008879

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: May 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed Kaposi's sarcoma (KS)

• HIV positive

• Evaluable disease involving the skin and/or viscera

• At least 5 lesions not previously treated with local therapy if restricted to the skin

• Pulmonary lesions evaluable by CT scan

• Gastrointestinal lesions evaluable by visualization or fiberoptic instrumentation

• Presence of at least one of the following indications for cytotoxic chemotherapy:

• Pulmonary involvement

• Visceral involvement

• Pain

• Edema

• Ulcerating lesions

• Decreased range of joint motion due to KS

• Multiple lesions not amenable to local therapy

• Lymphedema that impairs mobility or range of motion

• Significant psychological impact leading to social withdrawal

• Progressive disease within the past 3 weeks while receiving a stable regimen of highly active antiretroviral therapy for at least 4 weeks unless there is a need for urgent chemotherapy

• Prior participation on this study allowed, provided patient was removed from study due to non-pancreatic hyperamylasemia and the following are true:

• No dose-limiting toxicity by clinical and laboratory assessment

• Pancreatic amylase portion normal by fractionated amylase

• Lipase normal

• No symptoms referable to the pancreas

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 30-100%

Life expectancy:

• More than 2 months

Hematopoietic:

• Hemoglobin at least 9.0 g/dL

• Absolute neutrophil count at least 750/mm^3

• Platelet count at least 75,000/mm^3

Hepatic:

• Bilirubin no greater than 3.8 mg/dL with direct fraction no greater than 0.3 mg/dL and indirect fraction no greater than 3.5 mg/dL if due to protease inhibitor therapy

• PT or aPTT no greater than 120% of control unless due to lupus-type anticoagulant

• AST no greater than 2.5 times upper limit of normal

• No prior hepatic cirrhosis

• No hepatic dysfunction

Renal:

• Creatinine no greater than 1.5 mg/dL

• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No congestive heart failure

• Ejection fraction at least 40% by MUGA or echocardiogram

Other:

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception during and for 2 months after study participation

• No clinically significant autoimmune disease

• No active, gross gastrointestinal bleeding or uncontrolled peptic ulcer disease

• No prior inflammatory bowel disease

• No other prior or concurrent malignancy except squamous cell carcinoma in situ of the cervix or anus, completely resected basal cell carcinoma, or malignancy in complete remission for at least 1 year from the time a response was first documented

• No severe or life-threatening infection within the past 2 weeks

• No abnormality that would be scored as grade 3 toxicity except lymphopenia or direct manifestations of KS

• No known hypersensitivity to interleukin-12 (IL-12) or other compounds known to cross-react with IL-12

• No other medical condition that would preclude study entry

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• More than 2 weeks since prior cytokines or colony-stimulating factors other than epoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF)

• No prior combination interleukin-12 and doxorubicin HCl liposome except for patients previously treated on this protocol who are being enrolled for paclitaxel salvage therapy

• No concurrent immunomodulatory agents

• No concurrent cytokines except epoetin alfa or G-CSF

Chemotherapy:

• See Disease Characteristics

• See Biologic therapy

• At least 3 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas)

• More 6 months since prior suramin

• No other concurrent cytotoxic chemotherapy

Endocrine therapy:

• More than 2 months since prior systemic glucocorticoid steroids at doses sufficient to affect immune response (e.g., more than 20 mg of prednisone for more than 1 week)

• Concurrent replacement glucocorticoid therapy allowed

• No other concurrent systemic glucocorticoid therapy

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• Concurrent antiretroviral therapy required

• No other concurrent anti-KS therapy

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sarcoma
• Sarcoma, Kaposi

Intervention

Biological:
• recombinant interleukin-12

Drug:
• paclitaxel

• pegylated liposomal doxorubicin hydrochloride

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Little RF, Aleman K, Kumar P, Wyvill KM, Pluda JM, Read-Connole E, Wang V, Pittaluga S, Catanzaro AT, Steinberg SM, Yarchoan R. Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma. Blood. 200 — View Citation

Little RF, Aleman K, Merced K, et al.: Preliminary results of combination liposomal doxorubicin and interleukin-12 followed by chronic IL-12 maintenance therapy in advanced AIDS-related Kaposi's sarcoma. [Abstract] 10th Conference on Retroviruses and Oppo