Ignite Creation Date:
2024-05-05 @ 4:59 PM
Last Modification Date:
2024-10-26 @ 9:26 AM
Study NCT ID:
NCT00362310
Status:
COMPLETED
Last Update Posted:
2008-04-14
First Post:
2006-08-09
Brief Title:
Treatment of Classical Non-HIV-Related Kaposis Sarcoma With the Antiviral Drug Indinavir
Sponsor:
Istituto Superiore di SanitÃ
Organization:
Istituto Superiore di SanitÃ
Study Overview
Official Title:
A Phase II Trial With the HIV Protease Inhibitor Indinavir for the Treatment of Classical Kaposis Sarcoma
Status:
COMPLETED
Status Verified Date:
2008-04
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:
Recent studies have described a reduced incidence or the regression of Kaposis sarcoma KS in HIV-infected patients treated with the highly active anti-retroviral therapy HAART that contains at least one inhibitor of the HIV protease HIV-PI such as Indinavir Experimental studies have shown that part of the anti-KS actions of HIV-PI are not related to their antiretroviral actions but at least in part to their capability of blocking angiogenesis and tumor growth
This study will be conducted on HIV-negative classical KS patients to prove that Indinavir has anti-angiogenic and anti-KS effects in humans independently of its antiretroviral activity
This study will be conducted on HIV-negative classical KS patients to prove that Indinavir has anti-angiogenic and anti-KS effects in humans independently of its antiretroviral activity
Detailed Description:
Kaposis sarcoma KS is a rare vascular tumor affecting elderly individuals from Mediterranean countries CKS post transplant patients and with increased incidence and aggressiveness HIV-infected individuals AIDS-KS No definitive cure has been established for KS and all conventional therapies result in low response rate high toxicity and tumor relapse
Antiretroviral therapies including a HIV protease inhibitor HIV-PI have reduced AIDS-KS incidence and induce KS regression in treated patients This cannot be explained solely with drug-mediated HIV suppression and immune reconstitution We have shown that HIV-PI such as Indinavir or Saquinavir block KS-like lesions in mice by inhibiting angiogenesis and tumor cell invasion through a blockade of matrix metalloprotease 2 MMP2 proteolytic activation
Based on these data a proof-of-concept clinical study on HIV-negative classic KS C-KS patients was planned to prove that Indinavir has anti-angiogenic and anti-KS effects in humans independently of its antiretroviral activity
Recent concepts in the evaluation of non cytotoxic anti-cancer drugs such as anti-angiogenic agents suggest novel criteria for the design of clinical studies due to the specific mechanism of action of these drugs In particular the use of the conventional evaluation criteria based on cytotoxic actions may mislead the interpretation of the therapeutic efficacy of non cytotoxic agents The study was therefore designed to compare the clinical response to Indinavir in early-stage vs late-stage KS and by relating it to key biological endpoints and plasmatic drug concentrations This was also motivated by the rareness of C-KS and by ethical reasons which prevented the inclusion of a control group
Patients will be treated per os with 800 mg x 2daily of Indinavir for 12 months Follow-up will be one year
Primary objectives
Evaluation of the tumor response rate complete response partial response improved disease and stable disease to indinavir in the treatment of mild or severe classical KS patients Evaluation of the duration of response in indinavir-treated patients
Secondary objectives
Evaluation of Indinavir safety in classical KS population Determination of the pharmacokinetic profile of Indinavir Evaluation of key Kaposis sarcoma biological endpoints including markers of angiogenesis and tumor invasion Th1 and Th2 polarization of the immune response immunoactivation and immune responses to HHV8 herpesviruses and common pathogens
Antiretroviral therapies including a HIV protease inhibitor HIV-PI have reduced AIDS-KS incidence and induce KS regression in treated patients This cannot be explained solely with drug-mediated HIV suppression and immune reconstitution We have shown that HIV-PI such as Indinavir or Saquinavir block KS-like lesions in mice by inhibiting angiogenesis and tumor cell invasion through a blockade of matrix metalloprotease 2 MMP2 proteolytic activation
Based on these data a proof-of-concept clinical study on HIV-negative classic KS C-KS patients was planned to prove that Indinavir has anti-angiogenic and anti-KS effects in humans independently of its antiretroviral activity
Recent concepts in the evaluation of non cytotoxic anti-cancer drugs such as anti-angiogenic agents suggest novel criteria for the design of clinical studies due to the specific mechanism of action of these drugs In particular the use of the conventional evaluation criteria based on cytotoxic actions may mislead the interpretation of the therapeutic efficacy of non cytotoxic agents The study was therefore designed to compare the clinical response to Indinavir in early-stage vs late-stage KS and by relating it to key biological endpoints and plasmatic drug concentrations This was also motivated by the rareness of C-KS and by ethical reasons which prevented the inclusion of a control group
Patients will be treated per os with 800 mg x 2daily of Indinavir for 12 months Follow-up will be one year
Primary objectives
Evaluation of the tumor response rate complete response partial response improved disease and stable disease to indinavir in the treatment of mild or severe classical KS patients Evaluation of the duration of response in indinavir-treated patients
Secondary objectives
Evaluation of Indinavir safety in classical KS population Determination of the pharmacokinetic profile of Indinavir Evaluation of key Kaposis sarcoma biological endpoints including markers of angiogenesis and tumor invasion Th1 and Th2 polarization of the immune response immunoactivation and immune responses to HHV8 herpesviruses and common pathogens
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