Clinical trial NCT00000954: A Study of Chemotherapy Plus ddI or ddC in the Treatment of AIDS-Related Kaposi's Sarcoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sarcoma, Kaposi
HIV Infections
Keywords: 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
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Novum
name: Bristol-Myers Squibb
First posted: 2001-08-31
Enrollment: 72
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC CRS
state: California
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS
state: California
city: San Francisco
country: United States
facility: Ucsf Aids Crs
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Chicago
country: United States
facility: Rush Univ. Med. Ctr. ACTG CRS
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ. School of Medicine, Infectious Disease Research Clinic
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins Adult AIDS CRS
state: Maryland
city: Boston
country: United States
facility: Bmc Actg Crs
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington U CRS
state: Missouri
city: Buffalo
country: United States
facility: SUNY - Buffalo, Erie County Medical Ctr.
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Ctr.
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State Univ. AIDS CRS
state: Ohio
Study officials:
name: Mitsuyasu RT
role: STUDY_CHAIR
name: Gill PS
role: STUDY_CHAIR
References:
citation: 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
citation: 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)