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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00020449
First received: July 11, 2001
Last updated: June 18, 2013
Last verified: March 2004

July 11, 2001
June 18, 2013
January 2001
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Complete list of historical versions of study NCT00020449 on ClinicalTrials.gov Archive Site
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Liposomal Doxorubicin and Interleukin-12 in Treating Patients With AIDS-Related Kaposi's Sarcoma
A Phase II Study of Liposomal Doxorubicin and Interleukin-12 in AIDS-Associated Kaposi's Sarcoma Followed by Chronic Administration of Interleukin-12

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.

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.

Interventional
Phase 2
Masking: Open Label
Primary Purpose: Treatment
Sarcoma
  • Biological: recombinant interleukin-12
  • Drug: paclitaxel
  • Drug: pegylated liposomal doxorubicin hydrochloride
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
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May 2004
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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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00020449
CDR0000068502, NCI-01-C-0067, NCI-4010
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National Cancer Institute (NCI)
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Study Chair: Pallavi P. Kumar, MD NCI - HIV and AIDS Malignancy Branch
National Cancer Institute (NCI)
March 2004

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP