Paclitaxel Compared With Doxorubicin in Treating Patients With Advanced AIDS-Related Kaposi's Sarcoma
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Purpose
| 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 |
- 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.
- 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:
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:
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 (Adult, Senior) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00003350
| United States, Massachusetts | |
| Eastern Cooperative Oncology Group | |
| Boston, Massachusetts, United States, 02215 | |
| Principal Investigator: | Jamie Von Roenn | Eastern Cooperative Oncology Group |
More Information
| 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:
|
Sarcoma Sarcoma, Kaposi AIDS-Related Opportunistic Infections Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Herpesviridae Infections DNA Virus Infections Virus Diseases Neoplasms, Vascular Tissue Opportunistic Infections Infection HIV Infections Lentivirus Infections Retroviridae Infections |
RNA Virus Infections Parasitic Diseases Immunologic Deficiency Syndromes Immune System Diseases Paclitaxel Liposomal doxorubicin Albumin-Bound Paclitaxel Doxorubicin Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antibiotics, Antineoplastic |
ClinicalTrials.gov processed this record on September 27, 2016