To determine the toxicity and response to treatment with cytotoxic chemotherapy using doxorubicin (Adriamycin), bleomycin, and vincristine (DBV) for advanced AIDS-related Kaposi's sarcoma in combination with either didanosine (ddI) or zalcitabine (dideoxycytidine; ddC). AIDS patients with extensive Kaposi's sarcoma require treatment with effective cytotoxic agents to reduce the tumor burden, and they also require treatment with other possibly effective antiretroviral agents such as ddI or ddC to ameliorate (delay) the development of opportunistic infections.

Condition	Treatment or Intervention	Phase
Sarcoma, Kaposi HIV Infections	Drug: Bleomycin sulfate  Drug: Vincristine sulfate  Drug: Doxorubicin hydrochloride  Drug: Zalcitabine  Drug: Didanosine	Phase I

Further Study Details: 

Expected Total Enrollment:  72

AIDS patients with extensive Kaposi's sarcoma require treatment with effective cytotoxic agents to reduce the tumor burden, and they also require treatment with other possibly effective antiretroviral agents such as ddI or ddC to ameliorate (delay) the development of opportunistic infections.

In Phase I, eligible patients with advanced Kaposi's sarcoma are randomly assigned to either ddI or ddC in combination with DBV chemotherapy. On the average, patients receive 12-44 weeks of combined chemotherapy and antiretroviral therapy. If vincristine is deleted from Phase I because of excess neurotoxicity, it will not be administered as part of the combination chemotherapy if that treatment is continued in the Phase II study. The Phase II trial proceeds when at least six cycles (12 weeks) of DBV have been completed by six patients enrolled in Phase I, and an overall evaluation of tolerance to each combination treatment plan has been completed. Study medication is administered as in Phase I, with the possible deletion of vincristine. All patients who complete DBV chemotherapy with complete or partial response or stable disease will continue to receive the originally assigned investigational antiretroviral drug (ddC or ddI) for an additional 24 weeks.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Concurrent Medication: Required:

• Prophylaxis for Pneumocystis carinii pneumonia for all patients with CD4 cell counts < 200 cells/mm3.

Allowed:

• Chemoprophylaxis for candidiasis, MAC, and herpes simplex.
• Up to 14-day courses of metronidazole.
• Recombinant erythropoietin.
• Granulocyte-macrophage colony stimulating factor (GM-CSF) or granulocyte colony stimulating factor (G-CSF) for patients with ANC < 1000 cells/mm3.
• Isoniazid for treatment of tuberculosis, with permission of the protocol chair, when given in conjunction with pyridoxine.

Patients must have:

• HIV infection.
• Kaposi's sarcoma.

For patients < 18 years of age:

• consent of parent or guardian.

Exclusion Criteria

Co-existing Condition: Patients with the following symptoms or conditions are excluded:

• Opportunistic infection requiring treatment with myelosuppressive antibiotics (unless on G-CSF or GM-CSF).
• Other active malignancies except basal cell carcinoma of the skin or in situ cervical carcinoma.
• Prior history or current clinical evidence of peripheral neuropathy (= or > grade 1), pancreatitis, intractable diarrhea, or active seizure disorder not controlled by antiseizure medication.
• Significant pulmonary insufficiency (exertional dyspnea with minimal exertion, except that due to pulmonary Kaposi's sarcoma) or cardiac insufficiency (New York Heart Association status > 2).
• Neuropsychiatric history or altered mental status that would prevent informed consent or that would not permit compliance with this protocol.

Concurrent Medication: Excluded:

• Myelosuppressive antibiotics (unless on G-CSF or GM-CSF).
• Investigational agents other than drugs available on treatment IND and used for FDA sanctioned indications, or other antiviral, immunomodulating or antitumor drugs.
• Drugs associated with peripheral neuropathy (other than ddI, ddC, or vincristine), including hydralazine, disulfiram, nitrofurantoin, cisplatin, diethyldithiocarbamate, gold, rifampin, chloramphenicol, clioquinol, ethambutol, ethionamide, glutethimide, sodium cyanate, and thalidomide.

Patients with the following prior conditions or symptoms are excluded:

• Neuropsychiatric history or altered mental status that would prevent informed consent or that would not permit compliance with this protocol.

Prior Medication: Excluded:

• Systemic treatment with doxorubicin, bleomycin, or vincristine.
• Antitumor (Kaposi's sarcoma) drugs within 7 days of study entry.
• Any investigational drug (other than drugs available on treatment IND and used for FDA sanctioned indications) within 14 days of study entry.
• Neurotoxic drugs (other than ddI or ddC) within 30 days of study entry.
• Intralesional injections to a Kaposi's sarcoma marker lesion within 30 days of study entry.

Prior Treatment: Excluded:

• Irradiation of a Kaposi's sarcoma marker lesion within 30 days of study entry.

Alcohol consumption is strongly discouraged.

California
      San Francisco Gen Hosp, San Francisco,  California,  941102859,  United States
      UCLA CARE Ctr, Los Angeles,  California,  90095,  United States
      Univ of Southern California / LA County USC Med Ctr, Los Angeles,  California,  900331079,  United States
      K Norris Cancer Hosp / Los Angeles County - USC Med Ctr, Los Angeles,  California,  900331079,  United States
      Olive View Med Ctr, Sylmar,  California,  91342,  United States
Colorado
      Univ of Colorado Health Sciences Ctr, Denver,  Colorado,  80262,  United States
      Denver Dept of Health and Hosps, Denver,  Colorado,  80262,  United States
Illinois
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
Massachusetts
      Boston Med Ctr, Boston,  Massachusetts,  02118,  United States
New York
      SUNY - Stony Brook, Stony Brook,  New York,  117948153,  United States
      Mem Sloan - Kettering Cancer Ctr, New York,  New York,  10021,  United States
      Mount Sinai Med Ctr, New York,  New York,  10029,  United States
      Saint Luke's - Roosevelt Hosp Ctr, New York,  New York,  10025,  United States
      SUNY / Erie County Med Ctr at Buffalo, Buffalo,  New York,  14215,  United States
      Columbia Presbyterian Med Ctr, New York,  New York,  100323784,  United States
      Adirondack Med Ctr at Saranac Lake, Albany,  New York,  122083479,  United States
      Mid - Hudson Care Ctr, Albany,  New York,  122083479,  United States
      Albany Med College / Division of HIV Medicine A158, Albany,  New York,  122083479,  United States
North Carolina
      Univ of North Carolina, Chapel Hill,  North Carolina,  275997215,  United States
Ohio
      Ohio State Univ Hosp Clinic, Columbus,  Ohio,  432101228,  United States
Pennsylvania
      Girard Med Ctr, Philadelphia,  Pennsylvania,  191046073,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
Texas
      Univ of Texas Galveston, Galveston,  Texas,  775550435,  United States

Study chairs or principal investigators

Mitsuyasu RT,  Study Chair
Gill PS,  Study Chair

Study ID Numbers:  ACTG 163
Record last reviewed:  October 1996
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000954
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08