Treatment With Indinavir and Chemotherapy for Advanced Classical Kaposi's Sarcoma
Information source: Istituto Superiore di Sanità
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Kaposi's Sarcoma
Intervention: Indinavir in association with Vinblastina +/- Bleomicina (Drug)
Phase: Phase 2
Status: Active, not recruiting
Sponsored by: Barbara Ensoli, MD
Official(s) and/or principal investigator(s):
Lucia Brambilla, MD, Principal Investigator, Affiliation: Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy
The purpose of this study is to determine the clinical response to daily Indinavir oral
administration in association with a conventional chemotherapy based on cycles of systemic
Vinblastine +/- Bleomycin in patients affected by advanced classical (non HIV-associated)
Official title: Phase II Trial for the Treatment of Advanced Classical Kaposi's Sarcoma With the HIV Protease Inhibitor Indinavir in Combination With Chemotherapy
Study design: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: to determine the rate of complete responses at the end of treatment (including the maintenance phase) and of clinical responses after the maintenance phase, considering the residual debulked tumour (after the induction phase) as the reference point.
Secondary outcome: to determine time to tumor progression, treatment tolerability, indinavir pharmacokinetic profile, biological markers of response (ie. angiogenesis and immunoactivation parameters, HHV8 viral load and immune response)
It has been recently demonstrated that HIV protease inhibitors (HIV-PI) exert direct
anti-angiogenic and anti-tumor actions by blocking endothelial and tumor cell invasion and
matrix metalloprotease (MMP) activity. Based on this data, we have started a phase II trial
for the treatment of HIV-negative patients with CKS with the HIV-PI Indinavir. Indinavir was
well tolerated and induced KS regression/improvement in early-stage disease, and prolonged
stabilization in late-stage KS. Response required high plasma drug concentrations indicating
a "therapeutic" drug threshold, and was associated with a decrease of circulating
endothelial cells (CEC), basic fibroblast growth factor and MMP2 plasma levels. However,
large, confluent tumor masses were generally not responsive (Monini et al, AIDS 2009). Thus,
advanced KS may benefit at best by treatment with IND upon tumor debulking by conventional
Minimum age: 18 Years.
Maximum age: N/A.
- Documented diagnosis of KS
- Negative HIV ELISA test
- Being classified as stage III or IV
- Age â‰¥18 years
- Having interrupted any other anti-KS therapy since at least 2 weeks
- Being informed about the nature of the study and having signed the informed consent
- Inability to give informed consent
- Presence of other concomitant diseases, neoplasia (excluding cutaneous tumors with
limited extension and without diagnosis of melanoma) or any other life-threatening
clinical condition that would compromise its compliance to the protocol
- Concomitant treatments (within 2 weeks prior to the study) with systemic
immunomodulatory agents (i. e. glucocorticoids used as immunosuppressive agents,
interferons) or chemotherapy
- Monolateral nephropathy or history of nephrolithiasis during the last 5 years
- Any clinically relevant and persistent alteration of laboratory values observed
Locations and Contacts
Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy, Milan 20100, Italy
Principal Investigator (National AIDS Center, ISS) homepage
Ensoli B, StÃ¼rzl M, Monini P. Cytokine-mediated growth promotion of Kaposi's sarcoma and primary effusion lymphoma. Semin Cancer Biol. 2000 Oct;10(5):367-81. Review.
Sgadari C, Barillari G, Toschi E, Carlei D, Bacigalupo I, Baccarini S, Palladino C, Leone P, Bugarini R, Malavasi L, Cafaro A, Falchi M, Valdembri D, Rezza G, Bussolino F, Monini P, Ensoli B. HIV protease inhibitors are potent anti-angiogenic molecules and promote regression of Kaposi sarcoma. Nat Med. 2002 Mar;8(3):225-32.
Sgadari C, Monini P, Barillari G, Ensoli B. Use of HIV protease inhibitors to block Kaposi's sarcoma and tumour growth. Lancet Oncol. 2003 Sep;4(9):537-47. Review.
Monini P, Sgadari C, Toschi E, Barillari G, Ensoli B. Antitumour effects of antiretroviral therapy. Nat Rev Cancer. 2004 Nov;4(11):861-75. Review.
Monini P, Sgadari C, Grosso MG, Bellino S, Di Biagio A, Toschi E, Bacigalupo I, Sabbatucci M, Cencioni G, Salvi E, Leone P, Ensoli B. Clinical course of classic Kaposi's sarcoma in HIV-negative patients treated with the HIV protease inhibitor indinavir. AIDS. 2009 Feb 20;23(4):534-8. doi: 10.1097/QAD.0b013e3283262a8d.
Starting date: June 2008
Last updated: May 20, 2014