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

Sponsor

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

Overall Status

Completed

CT.gov ID

NCT00000954

Collaborator

Novum (Industry), Bristol-Myers Squibb (Industry)

Enrollment

Locations

5.1

Patients Per Site

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Sarcoma, Kaposi HIV Infections	Drug: Bleomycin sulfate Drug: Vincristine sulfate Drug: Doxorubicin hydrochloride Drug: Zalcitabine Drug: Didanosine	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

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

Actual Study Completion Date :

Sep 1, 1996

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC CRS	Los Angeles	California	United States	90033
2	UCLA CARE Center CRS	Los Angeles	California	United States	90095
3	Ucsf Aids Crs	San Francisco	California	United States
4	University of Colorado Hospital CRS	Aurora	Colorado	United States	80262
5	Northwestern University CRS	Chicago	Illinois	United States	60611
6	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois	United States
7	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana	United States	46202
8	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States
9	Bmc Actg Crs	Boston	Massachusetts	United States	02118
10	Washington U CRS	Saint Louis	Missouri	United States
11	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York	United States	14215
12	Memorial Sloan-Kettering Cancer Ctr.	New York	New York	United States	10021
13	Unc Aids Crs	Chapel Hill	North Carolina	United States	27599
14	The Ohio State Univ. AIDS CRS	Columbus	Ohio	United States	43210