Treatment With Indinavir and Chemotherapy for Advanced Classical Kaposi's Sarcoma

Condition(s) targeted: Kaposi's Sarcoma

Intervention: Indinavir in association with Vinblastina +/- Bleomicina (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Istituto Superiore di Sanita

Official(s) and/or principal investigator(s):
Lucia Brambilla, MD, Principal Investigator, Affiliation: Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy

Overall contact:
Barbara Ensoli, MD, PhD, Phone: +39-06-4990, Ext: 3209, Email: barbara.ensoli@iss.it

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) Kaposi's sarcoma

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)

Detailed description: 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 chemotherapy.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Documented diagnosis of KS

- Negative HIV ELISA test

- Being classified as stage III or IV

- Age ≥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

Exclusion Criteria:

- 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

- Pregnancy

- Monolateral nephropathy or history of nephrolithiasis during the last 5 years

- Any clinically relevant and persistent alteration of laboratory values observed

during screening

Barbara Ensoli, MD, PhD, Phone: +39-06-4990, Ext: 3209, Email: barbara.ensoli@iss.it

Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy, Milan 20100, Italy; Recruiting
Lucia Brambilla, MD, Phone: +39-02-55035115, Email: luciabrambilla1@virgilio.it
Biancamaria Scoppio, MD, Phone: +39-02-55035115, Email: marinellascoppio@tiscali.it
Lucia Brambilla, MD, Principal Investigator

Principal Investigator (National AIDS Center, ISS) homepage

Related publications:

Ensoli B, Stürzl 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. Antitumor effects of antiretroviral therapy. Nature Reviews Cancer, 4(11):861-75, 2004.

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.

Starting date: June 2008
Last updated: February 10, 2010