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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003350
First received: November 1, 1999
Last updated: January 9, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
AIDS-related Kaposi Sarcoma
Drug: paclitaxel
Drug: pegylated liposomal doxorubicin hydrochloride
Other: laboratory biomarker analysis
Procedure: quality-of-life assessment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Study of Paclitaxel Versus Liposomal Doxorubicin for the Treatment of Advanced AIDS-Associated Kaposi's Sarcoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Time from randomization to progression or to death from any cause, assessed up to 8 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Complete response rate [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Human immunodeficiency virus (HIV) infection assessed with respect to cluster of differentiation (CD)4 and CD8 lymphocyte subsets [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Relationship between viral load and response will be assessed.

  • HIV infection assessed with respect to HIV viral load [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Relationship between viral load and response will be assessed.


Estimated Enrollment: 240
Study Start Date: March 1999
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
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.

Drug: pegylated liposomal doxorubicin hydrochloride
Given IV
Other Names:
  • CAELYX
  • Dox-SL
  • DOXIL
  • doxorubicin hydrochloride liposome
  • LipoDox
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003350

Locations
United States, Massachusetts
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Investigators
Principal Investigator: Jamie Von Roenn Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003350     History of Changes
Other Study ID Numbers: NCI-2012-03149, E1D96, U10CA021115, CDR0000066331
Study First Received: November 1, 1999
Last Updated: January 9, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Sarcoma, Kaposi
AIDS-Related Opportunistic Infections
Sarcoma
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Herpesviridae Infections
DNA Virus Infections
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Vascular Tissue
Opportunistic Infections
Infection
Parasitic Diseases
Doxorubicin
Paclitaxel
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators

ClinicalTrials.gov processed this record on July 29, 2014