Clinical trial NCT00001114: The Safety and Effectiveness of Interferon Alfa-2B Plus Didanosine in Patients With Kaposi's Sarcoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoma, Kaposi
HIV Infections
Keywords: Sarcoma, Kaposi
Didanosine
Drug Interactions
Acquired Immunodeficiency Syndrome
Interferon-alpha
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Schering-Plough
name: Bristol-Myers Squibb
First posted: 2001-08-31
Enrollment: 90
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* 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.

Exclusion Criteria

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:

Excluded:

* 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:

Excluded:

* 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:

Excluded:

* 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:

Excluded:

* Radiation therapy within 30 days prior to study entry.

Risk Behavior:

* Alcohol consumption is strongly discouraged.
* Patients considered to be noncompliant should be excluded.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford 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: Boston
country: United States
facility: Bmc Actg Crs
state: Massachusetts
city: Saint Louis
country: United States
facility: St. Louis ConnectCare, Infectious Diseases Clinic
state: Missouri
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: Cincinnati
country: United States
facility: Univ. of Cincinnati CRS
state: Ohio
city: Philadelphia
country: United States
facility: Hosp. of the Univ. of Pennsylvania CRS
state: Pennsylvania
city: San Juan
country: Puerto Rico
facility: Puerto Rico-AIDS CRS
Study officials:
name: Krown SE
role: STUDY_CHAIR
References:
citation: Krown SE, Li P, Von Roenn JH, Paredes J, Huang J, Testa MA. Efficacy of low-dose interferon with antiretroviral therapy in Kaposi's sarcoma: a randomized phase II AIDS clinical trials group study. J Interferon Cytokine Res. 2002 Mar;22(3):295-303. doi: 10.1089/107999002753675712.