A Randomized Phase II Trial to Determine the Safety, Tolerance, and Efficacy of Two Doses of Interferon Alfa-2b Combined With Didanosine in Patients With Kaposi's Sarcoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 13
研究概览
简要总结
Primary: To evaluate the safety, toxicity, and antitumor activity of two doses of interferon alfa-2b (IFN-alpha) combined with a fixed dose of didanosine (ddI) in patients with Kaposi's sarcoma associated with HIV infection.
Secondary: To evaluate the effects of combined IFN-alpha and ddI treatment on HIV expression and markers of immune function.
Previous studies have shown that IFN-alpha can induce regression of Kaposi's sarcoma and suppression of HIV in some patients. Although various trials using IFN-alpha in combination with the nucleoside analogue zidovudine have demonstrated a high degree of antitumor activity and evidence of HIV suppression, the overlapping toxicity (primarily neutropenia) of these two agents has proven dose-limiting. The toxicity profile of ddI suggests that this drug may be better tolerated than zidovudine when combined with IFN-alpha.
详细描述
Previous studies have shown that IFN-alpha can induce regression of Kaposi's sarcoma and suppression of HIV in some patients. Although various trials using IFN-alpha in combination with the nucleoside analogue zidovudine have demonstrated a high degree of antitumor activity and evidence of HIV suppression, the overlapping toxicity (primarily neutropenia) of these two agents has proven dose-limiting. The toxicity profile of ddI suggests that this drug may be better tolerated than zidovudine when combined with IFN-alpha.
Up to 90 patients are randomized to receive either low or high doses of IFN-alpha (1 or 10 million Units/day) in combination with a fixed dose of ddI. Fourteen patients are initially entered at each dose level. If no objective antitumor responses are observed among the first 14 patients at a given dose, no further patients are entered on that treatment arm. If one or more antitumor responses are seen at a given dose, up to 45 patients may be entered on that treatment arm. Patients must complete at least 4 weeks of study therapy to be considered evaluable for tumor response. Treatment is continued until tumor progression or unacceptable toxicity occurs. PER AMENDMENT 9/19/96: NOTE - After 16 weeks of treatment subjects may receive any FDA approved antiretroviral drug regimen in addition to or in place of ddI.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Concurrent Medication:
- •Chemoprophylaxis for candidiasis and herpes simplex.
- •Up to 14 days of metronidazole.
- •Recombinant erythropoietin.
- •G-CSF (for severe cases of neutropenia).
- •Isoniazid for treatment of TB if given in conjunction with pyridoxine.
- •Required in patients with CD4 counts < 200 cells/mm3:
- •Prophylaxis for PCP.
- •PER AMENDMENT 9/19/96:
- •After the first 16 weeks of combined IFN alpha-2b and ddI treatment subjects may at the discretion of the investigator receive any FDA approved antiretroviral drug regimen in addition to or in place of ddI.
- •Patients must have:
- •Positive antibody to HIV.
- •Biopsy-proven Kaposi's sarcoma (at least 5 measurable lesions, with at least 1 measurable cutaneous lesion) involving the skin, lymph nodes, oral cavity, or asymptomatic lesions of the GI tract not requiring systemic chemotherapy. Lung involvement with Kaposi's sarcoma excludes.
- •Consent of parent or guardian if less than 18 years of age.
排除标准
- •Co-existing Condition:
- •Patients with the following symptoms and conditions are excluded:
- •Concurrent opportunistic infection or B symptoms including unexplained fever, night sweats, weight loss > 10 percent, and diarrhea lasting more than 2 weeks.
- •Visceral (non-nodal) Kaposi's sarcoma requiring cytotoxic chemotherapy.
- •Severe (> 2+) tumor-associated edema.
- •Concurrent neoplasia other than basal cell carcinoma, or anogenital intraepithelial neoplasia.
- •Current clinical evidence of peripheral neuropathy (= or > grade 1), pancreatitis, intractable diarrhea, or active seizure disorder not well controlled by anti-seizure medications.
- •Significant symptomatic cardiac disease.
- •Medical contraindication.
- •Concurrent Medication:
- •Other investigational, antiviral, immunomodulating, or antitumor agents.
- •Drugs associated with peripheral neuropathy (other than ddI).
- •PER AMENDMENT 9/19/96:
- •Other antiretroviral agents may not be taken during the first 16 weeks of combined IFN alpha-2b and ddI treatment.
- •Concurrent Treatment:
- •Radiation therapy.
- •Patients with the following prior conditions are excluded:
- •Opportunistic infection or B symptoms including unexplained fever, night sweats, weight loss > 10 percent, and diarrhea lasting more than 2 weeks.
- •Prior grade 3 or 4 toxicity attributed to ddI therapy.
- •Prior history of peripheral neuropathy (= or > grade 1), pancreatitis, intractable diarrhea, or active seizure disorder not well controlled by anti-seizure medications.
- •History of myocardial infarction or ventricular arrhythmias.
- •Prior Medication:
- •Prior IFN-alpha.
- •Corticosteroids, biological response modifiers, cytotoxic chemotherapy, or known neurotoxic drugs (other than ddI or ddC) within 30 days prior to study entry.
- •Therapy with antiretroviral drugs (other than ddI) within 7 days prior to study entry.
- •Prior Treatment:
- •Radiation therapy within 30 days prior to study entry.
- •Risk Behavior:
- •Alcohol consumption is strongly discouraged.
- •Patients considered to be noncompliant should be excluded.