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A Study of Chemotherapy Plus ddI or ddC in the Treatment of AIDS-Related Kaposi's Sarcoma
This study has been completed.
Sponsors and Collaborators: Novum
National Institute of Allergy and Infectious Diseases (NIAID)
Bristol-Myers Squibb
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000954
  Purpose

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

MedlinePlus related topics: AIDS Cancer Kaposi's Sarcoma Soft Tissue Sarcoma
Drug Information available for: Doxorubicin Doxorubicin hydrochloride Vincristine sulfate Vincristine Didanosine Zalcitabine Bleomycin Bleomycin sulfate
U.S. FDA Resources
Study Type: Interventional
Study Design: 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

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 72
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

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000954

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

Click here for more information about Zalcitabine  This link exits the ClinicalTrials.gov site
Click here for more information about Didanosine  This link exits the ClinicalTrials.gov site

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)

Study ID Numbers: ACTG 163
Study First Received: November 2, 1999
Last Updated: July 29, 2008
ClinicalTrials.gov Identifier: NCT00000954  
Health Authority: Unspecified

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Vincristine
Sarcoma, Kaposi
Zalcitabine
Didanosine
Doxorubicin
Drug Evaluation
Drug Interactions
Drug Therapy, Combination
Combined Modality Therapy
Acquired Immunodeficiency Syndrome
Antineoplastic Agents
Antineoplastic Agents, Combined
Antiviral Agents
Bleomycin

Study placed in the following topic categories:
Sexually Transmitted Diseases, Viral
Malignant mesenchymal tumor
Zalcitabine
Acquired Immunodeficiency Syndrome
Sarcoma, Kaposi
Vincristine
Bleomycin
Doxorubicin
Soft tissue sarcomas
Immunologic Deficiency Syndromes
Herpesviridae Infections
Virus Diseases
Neoplasms, Connective and Soft Tissue
Kaposi sarcoma
Didanosine
HIV Infections
Sexually Transmitted Diseases
Sarcoma
DNA Virus Infections
Retroviridae Infections

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antibiotics, Antineoplastic
Infection
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Neoplasms, Vascular Tissue
Nucleic Acid Synthesis Inhibitors
RNA Virus Infections
Neoplasms by Histologic Type
Anti-HIV Agents
Immune System Diseases
Mitosis Modulators
Enzyme Inhibitors
Antimitotic Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Tubulin Modulators
Lentivirus Infections
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 15, 2009