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

NCT ID: NCT00020449

Last Updated: 2013-06-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-01-31
• Study Completion Date: 2004-05-31

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.

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.

Conditions

Sarcoma

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

recombinant interleukin-12

Intervention Type: BIOLOGICAL

paclitaxel

Intervention Type: DRUG

pegylated liposomal doxorubicin hydrochloride

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Principal Investigators

Pallavi P. Kumar, MD

Role: STUDY_CHAIR

NCI - HIV and AIDS Malignancy Branch

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

Countries

United States

References

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. 2007 Dec 15;110(13):4165-71. doi: 10.1182/blood-2007-06-097568. Epub 2007 Sep 10.

Reference Type: RESULT

PMID: 17846226 (View on PubMed)

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 Opportunistic Infections, February 10-14, 2003, Boston, Massachusetts A-816, 2003.

Reference Type: RESULT

Other Identifiers

NCI-01-C-0067

Identifier Type: -

Identifier Source: secondary_id

NCI-4010

Identifier Type: -

Identifier Source: secondary_id

CDR0000068502

Identifier Type: -

Identifier Source: org_study_id

NCT00008879

Identifier Type: -

Identifier Source: nct_alias