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

Phase 2

Completed

• Conditions: Kaposi's Sarcoma

• Registration Number: NCT01067690
• Lead Sponsor: Barbara Ensoli, MD, PhD

Brief Summary

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

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.

Study Timeline

• Study Start: 2008-06
• Study First Submitted: 2010-02-10
• Study First Submitted QC: 2010-02-10
• Study First Posted: 2010-02-11
• Primary Completion: 2015-10
• Study Completion: 2016-06
• Status Verified: 2016-08
• Last Update Submitted: 2016-08-29
• Last Update Posted: 2016-08-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
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 Measures

Name	Time	Method
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)

Trial Locations

Locations (1)

Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy; 🇮🇹 Milan, Italy