Clinical trial NCT00001059: Comparison of Liposomal Doxorubicin Used Alone or in Combination With Bleomycin Plus Vincristine in the Treatment of Kaposi's Sarcoma in Patients With AIDS
Official title: Comparison Study of Liposomal Doxorubicin With or Without Bleomycin and Vincristine for the Treatment of Advanced AIDS-Associated Kaposi's Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoma, Kaposi
HIV Infections
Keywords: Vincristine
Sarcoma, Kaposi
Liposomes
Doxorubicin
Drug Therapy, Combination
Granulocyte Colony-Stimulating Factor
Acquired Immunodeficiency Syndrome
Bleomycin
Drug Carriers
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Sequus Pharmaceuticals
name: Amgen
First posted: 2001-08-31
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

Detailed description: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Therapeutics CRS
state: Alabama
city: Los Angeles
country: United States
facility: USC CRS
state: California
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS
state: California
city: San Francisco
country: United States
facility: Ucsf Aids Crs
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Miami
country: United States
facility: Univ. of Miami AIDS CRS
state: Florida
city: Honolulu
country: United States
facility: Queens Med. Ctr.
state: Hawaii
city: Honolulu
country: United States
facility: Univ. of Hawaii at Manoa, Leahi Hosp.
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Chicago
country: United States
facility: Rush Univ. Med. Ctr. ACTG CRS
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ. School of Medicine, Infectious Disease Research Clinic
state: Indiana
city: Boston
country: United States
facility: Bmc Actg Crs
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess - East Campus A0102 CRS
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital ACTG CRS
state: Massachusetts
city: St. Louis
country: United States
facility: Washington U CRS
state: Missouri
city: Buffalo
country: United States
facility: SUNY - Buffalo, Erie County Medical Ctr.
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Ctr.
state: New York
Study officials:
name: Mitsuyasu R
role: STUDY_CHAIR
name: Krown S
role: STUDY_CHAIR
name: Von Roenn JH
role: STUDY_CHAIR
References:
citation: Mitsuyasu R, et al. Comparison study of liposomal doxorubicin (DOX) alone or with bleomycin and vincristine (DBV) for treatment of advanced AIDS-associated Kaposi's sarcoma (AIDS-KS): AIDS Clinical Trial Group (ACTG) protocol 286 (meeting abstract). Proc Annu Meet Am Soc Clin Oncol. 1997;16:A191