The Safety and Effectiveness of Interferon Alfa-2B Plus Didanosine in Patients With Kaposi's Sarcoma

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00001114

Collaborator

Schering-Plough (Industry), Bristol-Myers Squibb (Industry)

Enrollment

Locations

6.9

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma, Kaposi HIV Infections	Drug: Interferon alfa-2b Drug: Didanosine	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

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

Actual Study Completion Date :

Mar 1, 2000

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford CRS	Palo Alto	California	United States	94115
2	University of Colorado Hospital CRS	Aurora	Colorado	United States	80262
3	Northwestern University CRS	Chicago	Illinois	United States	60611
4	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois	United States	60612
5	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana	United States	46202
6	Bmc Actg Crs	Boston	Massachusetts	United States	02118
7	St. Louis ConnectCare, Infectious Diseases Clinic	Saint Louis	Missouri	United States	63112
8	Washington U CRS	Saint Louis	Missouri	United States
9	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York	United States	14215
10	Memorial Sloan-Kettering Cancer Ctr.	New York	New York	United States	10021
11	Univ. of Cincinnati CRS	Cincinnati	Ohio	United States	45267
12	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania	United States	19104
13	Puerto Rico-AIDS CRS	San Juan		Puerto Rico	00936