A Study of Chemotherapy Plus ddI or ddC in the Treatment of AIDS-Related Kaposi's Sarcoma
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
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: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s): Mitsuyasu RT, Study Chair Gill PS, Study Chair
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.
Clinical Details
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: Primary Purpose: 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.
Eligibility
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.
Locations and Contacts
UCLA CARE Center CRS, Los Angeles, California 90095, United States
USC CRS, Los Angeles, California 90033, United States
Ucsf Aids Crs, San Francisco, California, United States
University of Colorado Hospital CRS, Aurora, Colorado 80262, United States
Northwestern University CRS, Chicago, Illinois 60611, United States
Rush Univ. Med. Ctr. ACTG CRS, Chicago, Illinois, United States
Indiana Univ. School of Medicine, Infectious Disease Research Clinic, Indianapolis, Indiana 46202, United States
Johns Hopkins Adult AIDS CRS, Baltimore, Maryland, United States
Bmc Actg Crs, Boston, Massachusetts 02118, United States
Washington U CRS, St. Louis, Missouri, United States
SUNY - Buffalo, Erie County Medical Ctr., Buffalo, New York 14215, United States
Memorial Sloan-Kettering Cancer Ctr., New York, New York 10021, United States
Unc Aids Crs, Chapel Hill, North Carolina 27599, United States
The Ohio State Univ. AIDS CRS, Columbus, Ohio 43210, United States
Additional Information
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: March 30, 2012
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