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

June 18, 2013 updated by: National Cancer Institute (NCI)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Study Chair: Pallavi P. Kumar, MD, NCI - HIV and AIDS Malignancy Branch

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2001

Study Completion (Actual)

May 1, 2004

Study Registration Dates

First Submitted

July 11, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

June 19, 2013

Last Update Submitted That Met QC Criteria

June 18, 2013

Last Verified

March 1, 2004

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000068502
  • NCI-01-C-0067
  • NCI-4010

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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