Clinical Trial: Paclitaxel Compared With Doxorubicin in Treating Patients With Advanced AIDS-Related Kaposi's Sarcoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase III Study of Paclitaxel Versus Liposomal Doxorubicin for the Treatment of Advanced AIDS-Associated Kaposi's Sarcoma

Brief Summary: Randomized phase III trial to compare the effectiveness of paclitaxel with that of doxorubicin in treating patients who have advanced AIDS-related Kaposi's sarcoma. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether paclitaxel is more effective than doxorubicin in treating patients with advanced AIDS-related Kaposi's sarcoma

Detailed Summary:

PRIMARY OBJECTIVES:

I. To compare the effect of therapy with paclitaxel to therapy with liposomal doxorubicin on progression-free survival and on global assessment of quality of life of subjects with advanced AIDS-related K.S.

II. To compare the toxicity profile of intravenous paclitaxel with liposomal doxorubicin in patients with advanced AIDS-related K.S.

III. To compare the overall and complete response rate of intravenous paclitaxel with liposomal doxorubicin in patients with advanced AIDS-related K.S.

IV. To evaluate the effect of intravenous paclitaxel as compared with therapy with liposomal doxorubicin on the clinical course of HIV infection in patients with advanced AIDS-related K.S., by monitoring CD4 and CD8 lymphocyte subsets, HIV viral load and the incidence and type of opportunistic infections.

V. To explore the relationship between viral load and response to the therapy for patients with AIDS-related K.S.

VI. To describe the relationship between "technical" response as measured by the current KS response criteria and the clinical benefit of therapy as measured by the revised KS clinical benefit criteria.

OUTLINE: This is a randomized study. Patients are randomized to receive either paclitaxel (arm I) or doxorubicin HCL liposome(arm II).

Arm I: Patients receive paclitaxel over 3 hours by intravenous infusion. Treatment course repeats every 2 weeks. Patients are evaluated every third course.

Arm II: Patients receive doxorubicin HCL liposome over 30-60 minute
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Progression-free survival [ Time Frame: Time from randomization to progression or to death from any cause, assessed up to 8 years ]

The group sequential method by O'Brien and Fleming for the two-sided test will be used. The significance level will be based on the type I error spending function of Lan and DeMets such that the overall significance level will be maintained at 0.05.


Original Primary Outcome:

Current Secondary Outcome:

  • Patients' health related quality of life (QOL) in terms of change in pain score, edema-related mobility, gastrointestinal (GI) symptoms and respiratory symptoms based on the total score from the Functional Assessment of HIV Infection (FAHI) v3 [ Time Frame: Up to 8 years ]
    The relationship between the clinical benefits and the responses measured by the current Kaposi's sarcoma (KS) response criteria as well as the clinical benefits and the standard QOL assessments will be described. Difference in linear temporal trends in QOL across treatment groups compared using mixed effects linear regression models. Polynomial terms will be incorporated into the models if a linear relationship does not adequately account for the temporal trends in QOL.
  • Overall response rate [ Time Frame: Up to 8 years ]
  • Complete response rate [ Time Frame: Up to 8 years ]
  • Toxicities in terms of nausea/vomiting, alopecia, neuropathy and mouth sores, based on the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 [ Time Frame: Up to 8 years ]
  • Human immunodeficiency virus (HIV) infection assessed with respect to cluster of differentiation (CD)4 and CD8 lymphocyte subsets [ Time Frame: Baseline ]
    Relationship between viral load and response will be assessed.
  • HIV infection assessed with respect to HIV viral load [ Time Frame: Baseline ]
    Relationship between viral load and response will be assessed.
  • HIV infection assessed with respect to incidence and type of opportunistic infections [ Time Frame: Up to 8 years ]
    Relationship between viral load and response will be assessed.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: November 1, 1999
Date Started: March 1999
Date Completion:
Last Updated: January 9, 2013
Last Verified: January 2013