Comparison of Liposomal Doxorubicin Used Alone or in Combination With Bleomycin Plus Vincristine in the Treatment of Kaposi's Sarcoma in Patients With AIDS

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00001059

Collaborator

Sequus Pharmaceuticals (Industry), Amgen (Industry)

120

Enrollment

Locations

7.1

Patients Per Site

Study Details

Study Description

Brief Summary

To evaluate the safety and efficacy of liposomal doxorubicin hydrochloride ( DOX-SL ) alone or in combination with bleomycin and vincristine in the long-term treatment of AIDS-related Kaposi's sarcoma. To determine whether the 3-drug combination enhances progression-free survival and quality of life.

Liposomal formulations of chemotherapeutic agents increase drug accumulation in tumors, which permits disease palliation at relatively low doses and thus decreases some of the dose-limiting toxicity. Multi-agent therapy is considered to be more effective than single-agent therapy; therefore, DOX-SL will be combined with bleomycin and vincristine.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma, Kaposi HIV Infections	Drug: Doxorubicin hydrochloride (liposomal) Drug: Filgrastim Drug: Bleomycin sulfate Drug: Vincristine sulfate	Phase 2

Detailed Description

Patients are randomized to receive intravenous DOX-SL alone or in combination with vincristine/bleomycin every 2 weeks. Filgrastim ( granulocyte colony-stimulating factor; G-CSF ) may be given as needed for neutropenia.

AS PER AMENDMENT 11/7/96: Based on interim review data, it is recommended that subjects receiving DOX-SL plus vincristine/bleomycin have vincristine/bleomycin discontinued and receive DOX-SL alone unless, in the opinion of the treating physician, they are benefitting from the DOX-SL plus vincristine/bleomycin regimen.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

Comparison Study of Liposomal Doxorubicin With or Without Bleomycin and Vincristine for the Treatment of Advanced AIDS-Associated Kaposi's Sarcoma

Actual Study Completion Date :

Aug 1, 1998

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Concurrent Medication:

Allowed:

G-CSF.
Licensed or Treatment IND-approved antiretrovirals ( AZT, ddI, ddC, d4T ).
PCP prophylaxis (required if CD4 count < 200 cells/mm3).
Chemoprophylaxis or maintenance for bacterial infections, candidiasis, MAC, and herpes simplex.
Up to 14 days of metronidazole.
Recombinant erythropoietin.

Patients must have:

Documented HIV infection.
Advanced stage Kaposi's sarcoma.
No active acute opportunistic infection.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

Significant pulmonary insufficiency (unless due to pulmonary KS).
Significant cardiac insufficiency.
Other active malignancies except for basal or squamous cell carcinoma of the skin or in situ cervical cancer.
Grade 2 or worse peripheral neuropathy.
Altered mental status that prevents informed consent.
Active Mycobacterium tuberculosis.
Hypersensitivity or allergic reaction to any study drugs or E. coli-derived medications such as filgrastim (G-CSF).

Concurrent Medication:

Excluded:

GM-CSF.
Drugs associated with peripheral neuropathy (other than approved antiretrovirals and vincristine).
Multi-drug therapy for active Mycobacterium tuberculosis (although isoniazid and pyridoxine is allowed as treatment for a positive PPD, with permission of study chair).

Concurrent Treatment:

Excluded:

Radiation therapy to study marker lesions.

Patients with the following prior condition are excluded:

Neuropsychiatric history.

Prior Medication:

Excluded:

Any anti-KS therapy within 21 days prior to study entry.
Prior systemic therapy with any anthracycline (including liposomal anthracyclines), vincristine, or bleomycin.
Any investigational drug (other than those available through Treatment IND and used for FDA-sanctioned purposes) within 14 days prior to study entry.

PER AMENDMENT 11/29/95:

No more than 2 cycles of any systemic chemotherapy for Kaposi's sarcoma.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Therapeutics CRS	Birmingham	Alabama	United States	35294
2	USC CRS	Los Angeles	California	United States	90033
3	UCLA CARE Center CRS	Los Angeles	California	United States	90095
4	Ucsf Aids Crs	San Francisco	California	United States
5	University of Colorado Hospital CRS	Aurora	Colorado	United States	80262
6	Univ. of Miami AIDS CRS	Miami	Florida	United States	33136
7	Queens Med. Ctr.	Honolulu	Hawaii	United States	96813
8	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii	United States	96816
9	Northwestern University CRS	Chicago	Illinois	United States	60611
10	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois	United States	60612
11	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana	United States	46202
12	Bmc Actg Crs	Boston	Massachusetts	United States	02118
13	Beth Israel Deaconess - East Campus A0102 CRS	Boston	Massachusetts	United States	02215
14	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts	United States
15	Washington U CRS	St. Louis	Missouri	United States	63110
16	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York	United States	14215
17	Memorial Sloan-Kettering Cancer Ctr.	New York	New York	United States	10021