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

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

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

Study Overview

• Status: Completed
• Conditions: AIDS-related Kaposi Sarcoma
• Intervention / Treatment: Other: laboratory biomarker analysis; Procedure: quality-of-life assessment; Drug: paclitaxel; Drug: pegylated liposomal doxorubicin hydrochloride

Detailed Description

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 minutes by intravenous infusion. Treatment course is repeated every 3 weeks. Patients are evaluated before every odd course.

Patients in both arms continue treatment if there is no disease progression or unacceptable toxicity. Patients with complete response continue on study treatment for 2 courses beyond documented complete response.

Quality of life is assessed before, during, and after treatment.

Patients are followed every 3 months for the first 2 years, then every 6 months for years 2-5, and then annually thereafter.

PROJECTED ACCRUAL: There will be 240 patients (120 patients in each arm) accrued into this study over 24 months.

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Eastern Cooperative Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Serologic diagnosis of HIV infection as documented by a positive ELISA and confirmed with a western blot, other federally approved HIV diagnostic test, or HIV viral load measurement

• Biopsy-proven, measurable Kaposi's sarcoma with any of the following:

  • Progressive cutaneous disease
  • Symptomatic oropharyngeal or conjunctival lesions
  • Any visceral involvement
  • Tumor-related lymphedema
  • Tumor-related ulceration or pain
  • NOTE: All patients must have measurable disease; baseline measurements must be obtained < 4 weeks prior to registration
• ECOG performance status 0-2
• ANC >= 1000/mm³ (with or without the use of colony-stimulating factors)
• Platelet count >= 50,000/mm³
• Hemoglobin >= 8 gm/dL
• Bilirubin < 1.5 x the upper limit of normal (unless elevation is due to Crixivan administration with isolated elevation in conjugated bilirubin)
• SGOT or SGPT =< 5 x the upper limit of normal
• Creatinine =< 2.1 mg/dl
• Women must not be pregnant or lactating due to potential toxicity of therapy
• Women of childbearing potential and sexually active men must be advised to use an accepted and effective method of contraception due to potential toxicity of therapy
• No prior systemic cytotoxic chemotherapy for Kaposi's sarcoma
• Prior radiation therapy must have been discontinued >= 7 days prior to randomization and must NOT have been delivered to marker lesions; (NOTE: Radiation therapy will not be permitted during study treatment)
• No active, untreated infection (no new opportunistic infectious complications within the previous week requiring a change in antibiotics); maintenance therapy for opportunistic infections will be allowed
• No prior or concomitant malignancy other than curatively treated carcinoma in situ of the cervix or basal/squamous cell carcinoma of the skin
• No neuropsychiatric history or altered mental status that might prevent informed consent or affect the ability of the patient to comply with the study
• Institutions must ask patients to participate in the quality of life portion of the protocol; however, patients may decline participation in this component of the study and still be eligible; the reason for refusal or inability to complete the QOL assessments must be documented in the Assessment Compliance Form (#596)
• Must not be known to be sensitive to E. coli derived proteins
• No history of cardiac insufficiency (NY Heart Association status >= 2)
• Patients must be on stable (no change in drugs or doses) antiretroviral therapy for greater than 14 days prior to study; a combination regimen is required; ideally this will be a protease inhibitor containing triple therapy regimen
• Patients must give signed, written informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (paclitaxel); Patients receive paclitaxel over 3 hours by intravenous infusion. Treatment course repeats every 2 weeks. Patients are evaluated every third course. Patients in both arms continue treatment if there is no disease progression or unacceptable toxicity. Patients with complete response continue on study treatment for 2 courses beyond documented complete response. Quality of life is assessed before, during, and after treatment.	Other: laboratory biomarker analysis; Correlative studies; Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment; Drug: paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; TAX
Experimental: Arm II (pegylated liposomal doxorubicin hydrochloride); Patients receive doxorubicin HCL liposome over 30-60 minutes by intravenous infusion. Treatment course is repeated every 3 weeks. Patients are evaluated before every odd course. Patients in both arms continue treatment if there is no disease progression or unacceptable toxicity. Patients with complete response continue on study treatment for 2 courses beyond documented complete response. Quality of life is assessed before, during, and after treatment.	Other: laboratory biomarker analysis; Correlative studies; Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment; Drug: pegylated liposomal doxorubicin hydrochloride; Given IV; Other Names: doxorubicin hydrochloride liposome; LipoDox; Dox-SL; CAELYX; DOXIL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	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.	Time from randomization to progression or to death from any cause, assessed up to 8 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Up to 8 years
Overall response rate		Up to 8 years
Complete response rate		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		Up to 8 years
Human immunodeficiency virus (HIV) infection assessed with respect to cluster of differentiation (CD)4 and CD8 lymphocyte subsets	Relationship between viral load and response will be assessed.	Baseline
HIV infection assessed with respect to HIV viral load	Relationship between viral load and response will be assessed.	Baseline
HIV infection assessed with respect to incidence and type of opportunistic infections	Relationship between viral load and response will be assessed.	Up to 8 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jamie Von Roenn, Eastern Cooperative Oncology Group

Study record dates

Study Major Dates

• Study Start: March 1, 1999
• Primary Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: July 10, 2003
• First Posted (Estimate): July 11, 2003

Study Record Updates

• Last Update Posted (Estimate): January 10, 2013
• Last Update Submitted That Met QC Criteria: January 9, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; DNA Virus Infections; Herpesviridae Infections; Neoplasms, Vascular Tissue; Sarcoma; Sarcoma, Kaposi; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Paclitaxel; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: NCI-2012-03149; U10CA021115 (U.S. NIH Grant/Contract); E1D96; CDR0000066331 (Registry Identifier: PDQ (Physician Data Query))