Ignite Creation Date:
2024-05-05 @ 4:39 PM
Last Modification Date:
2024-10-26 @ 9:22 AM
Study NCT ID:
NCT00287495
Status:
TERMINATED
Last Update Posted:
2019-12-12
First Post:
2006-02-04
Brief Title:
BAY 43-9006 Sorafenib to Treat Patients With Kaposis Sarcoma
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase I and Pharmacokinetic Study of BAY 43-9006 Sorafenib in Patients With Kaposis Sarcoma
Status:
TERMINATED
Status Verified Date:
2017-10-18
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Kaposis sarcoma KS is a disease in which cancer cells are found in the tissues under the skin or mucous membranes that line the mouth nose and anus KS causes red or purple patches lesions on the skin or mucous membranes and spreads to other organs in the body such as the lungs liver or intestinal tract
BAY 43-9006 inhibits the activity of several proteins or protein receptors in cells that are thought to be important to the progression of KS Blocking these mechanisms may cause KS to get better
Objectives
To learn about the toxicity and blood levels of BAY 43-9006 in people with KS who are and are not taking the anti-retroviral drug ritonavir
To look for evidence of a beneficial treatment effect of BAY 43-9006
Eligibility
Adults with confirmed KS both HIV-positive and HIV-negative
Patients must have either 1 at least five measurable KS lesions with no previous local therapy or 2 other measurable non-skin disease that permits evaluation of a response to treatment
Design
Patients are randomly assigned to a specific dose of BAY 43-9006 They take the drug by mouth either once or twice daily depending on their dose group for up to 54 weeks
Drug blood levels are determined after patients have been taking BAY 43-9006 for 1 to 2 weeks by blood collections immediately before the dose and at 1 2 4 8 12 16 and 24 hours after the dose
Patients are evaluated every 3 weeks with review of a medication diary interview about drug side effects physical examination and assessment of KS lesions
KS lesions are photographed on entering the study and at other time points during the study
CD4 cell counts and HIV viral load are tested every 12 weeks
Biopsies are done at the start of the study on day 15 and if it appears that all of the lesions have resolved
Other procedures such as CT or MRI scans may be done if medically indicated
Kaposis sarcoma KS is a disease in which cancer cells are found in the tissues under the skin or mucous membranes that line the mouth nose and anus KS causes red or purple patches lesions on the skin or mucous membranes and spreads to other organs in the body such as the lungs liver or intestinal tract
BAY 43-9006 inhibits the activity of several proteins or protein receptors in cells that are thought to be important to the progression of KS Blocking these mechanisms may cause KS to get better
Objectives
To learn about the toxicity and blood levels of BAY 43-9006 in people with KS who are and are not taking the anti-retroviral drug ritonavir
To look for evidence of a beneficial treatment effect of BAY 43-9006
Eligibility
Adults with confirmed KS both HIV-positive and HIV-negative
Patients must have either 1 at least five measurable KS lesions with no previous local therapy or 2 other measurable non-skin disease that permits evaluation of a response to treatment
Design
Patients are randomly assigned to a specific dose of BAY 43-9006 They take the drug by mouth either once or twice daily depending on their dose group for up to 54 weeks
Drug blood levels are determined after patients have been taking BAY 43-9006 for 1 to 2 weeks by blood collections immediately before the dose and at 1 2 4 8 12 16 and 24 hours after the dose
Patients are evaluated every 3 weeks with review of a medication diary interview about drug side effects physical examination and assessment of KS lesions
KS lesions are photographed on entering the study and at other time points during the study
CD4 cell counts and HIV viral load are tested every 12 weeks
Biopsies are done at the start of the study on day 15 and if it appears that all of the lesions have resolved
Other procedures such as CT or MRI scans may be done if medically indicated
Detailed Description:
BACKGROUND This study is designed to test the toxicity and pharmacokinetics of different doses of BAY 43-9006 Sorafenib in patients with Kaposi s sarcoma KS It will also assess in a preliminary manner the activity of BAY 43-9006 in this disease and its effect on biological markers BAY 43-9006 is a potent inhibitor of wild-type and mutant c-Raf kinase isoforms In addition this agent also inhibits p38 c-kit vascular endothelial growth factor receptor 2VEGFR2 VEGF-R3 and platelet derived growth factor receptor beta PDGFR-B There is evidence that several of these receptors and especially VEGF-R2 VEGF-R3 and PDGF-RB are important in KS pathogenesis The principle tumor cells of KS lesions are spindle cells which are derived from endothelial cells Spindle cells proliferate in response to VEGF VEGF-C a ligand for VEGF-R3 and PDGF and the stimulation of spindle cells by these factors appears to be an important component in the pathogenesis of KS There is also evidence that c-kit is important in KS Because BAY 43-9006 can inhibit the function of these receptors and c-kit it may have specific activity against this tumor BAY 43-9006 is metabolized at least in part by CYP 3A4 and ritonavir an HIV protease inhibitor commonly used in AIDS patients is an inhibitor of CYP 3A4 Also AIDS patients are often quite sensitive to drug toxicities Thus patients with AIDS-KS on ritonavir may be particularly sensitive to BAY 43-9006
OBJECTIVES To assess the toxicity profile and pharmacokinetics of BAY 43-9006 at oral dose regimens of 200 mg once daily 200mg twice daily or 400 mg twice daily up to the toxic dose in patients with HIV-associated Kaposi s sarcoma KS who are receiving ritonavir Also to assess in a preliminary manner the pharmacokinetics and toxicity profile of BAY 43-9006 in patients who are not receiving ritonavir
ELIGIBILITY Key eligibility criteria are as follows patients 18 years of age or older with or without HIV infection and with KS and at least 5 cutaneous lesions untreated by local therapy patients with HIV infection must have KS that is progressing or stable on highly active antiretroviral therapy HAART patients with extensive active visceral or symptomatic KS are excluded
DESIGN Patients with AIDS-KS who are receiving ritonavir will be administered BAY 43-9006 An initial group of patients will be administered 200 mg BAY 43-9006 once daily and subsequent groups will receive 200 mg twice daily and 400 mg twice daily respectively Also two groups of patients with KS and not on ritonavir will be administered 200 mg and 400 mg BAY 43-9006 twice daily respectively Patients will be studied for toxicity pharmacokinetics KS response the effect on biological markers such as target receptor kinase phosphorylation and signaling molecules in KS tissue Other parameters that will be assessed will include VEGF levels the viral load of KSHV and KS lesion blood flow by non-invasive techniques If patients tolerate BAY 43-9006 they will receive it for up to 24 weeks If they have evidence of stable KS or a tumor response they may receive the drug for up to 54 weeks total
OBJECTIVES To assess the toxicity profile and pharmacokinetics of BAY 43-9006 at oral dose regimens of 200 mg once daily 200mg twice daily or 400 mg twice daily up to the toxic dose in patients with HIV-associated Kaposi s sarcoma KS who are receiving ritonavir Also to assess in a preliminary manner the pharmacokinetics and toxicity profile of BAY 43-9006 in patients who are not receiving ritonavir
ELIGIBILITY Key eligibility criteria are as follows patients 18 years of age or older with or without HIV infection and with KS and at least 5 cutaneous lesions untreated by local therapy patients with HIV infection must have KS that is progressing or stable on highly active antiretroviral therapy HAART patients with extensive active visceral or symptomatic KS are excluded
DESIGN Patients with AIDS-KS who are receiving ritonavir will be administered BAY 43-9006 An initial group of patients will be administered 200 mg BAY 43-9006 once daily and subsequent groups will receive 200 mg twice daily and 400 mg twice daily respectively Also two groups of patients with KS and not on ritonavir will be administered 200 mg and 400 mg BAY 43-9006 twice daily respectively Patients will be studied for toxicity pharmacokinetics KS response the effect on biological markers such as target receptor kinase phosphorylation and signaling molecules in KS tissue Other parameters that will be assessed will include VEGF levels the viral load of KSHV and KS lesion blood flow by non-invasive techniques If patients tolerate BAY 43-9006 they will receive it for up to 24 weeks If they have evidence of stable KS or a tumor response they may receive the drug for up to 54 weeks total
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 06-C-0083 | None | None | None |