A Study of Chemotherapy Plus ddI or ddC in the Treatment of AIDS-Related Kaposi's Sarcoma

Condition(s) targeted: Sarcoma, Kaposi; HIV Infections

Intervention: Bleomycin sulfate (Drug); Vincristine sulfate (Drug); Doxorubicin hydrochloride (Drug); Zalcitabine (Drug); Didanosine (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Novum

Official(s) and/or principal investigator(s):
Mitsuyasu RT, Study Chair
Gill PS, Study Chair

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.

Official title: Phase I/II Study of Combination Chemotherapy (Adriamycin, Bleomycin, +/- Vincristine) and Dideoxyinosine (ddI) or Dideoxycytidine (ddC) in the Treatment of AIDS-Related Kaposi's Sarcoma

Study design: Treatment

Detailed description: 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.

Minimum age: 13 Years. Maximum age: N/A. Gender(s): 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.

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

Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States

Denver Dept of Health and Hosps, Denver, Colorado 80262, United States

Northwestern Univ Med School, Chicago, Illinois 60611, United States

Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States

Boston Med Ctr, Boston, Massachusetts 02118, United States

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

Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States

Ohio State Univ Hosp Clinic, Columbus, Ohio 432101228, United States

Girard Med Ctr, Philadelphia, Pennsylvania 191046073, United States

Julio Arroyo, West Columbia, South Carolina 29169, United States

Univ of Texas Galveston, Galveston, Texas 775550435, United States

Click here for more information about Zalcitabine

Click here for more information about Didanosine

Related publications:

Mitsuyasu R, et al. Combination chemotherapy, adriamycin, bleomycin, vincristine (ABV) with dideoxyinosine (ddI) or dideoxycytidine (ddC) in advanced AIDS-related Kaposi's sarcoma (ACTG 163). Proc Annu Meet Am Assoc Cancer Res. 1995;14:A822

Mitsuyasu R, Gill P, Paredes J, Ambinder R, Ratner L, Feldstein M. Preliminary results of a phase I/II trial of combination chemotherapy (ABV) with ddI or ddC in AIDS-related Kaposi's sarcoma (ACTG 163). Int Conf AIDS. 1993 Jun 6-11;9(1):396 (abstract no PO-B12-1565)

Last updated: June 23, 2005