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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00020449

Collaborator

(none)

Location

Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma	Biological: recombinant interleukin-12 Drug: paclitaxel Drug: pegylated liposomal doxorubicin hydrochloride	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jan 1, 2001

Actual Study Completion Date :

May 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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