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

Barbara Ensoli, MD, PhD

Status and phase

Completed

Phase 2

Conditions

Kaposi's Sarcoma

Treatments

Drug: Indinavir in association with Vinblastina +/- Bleomicina

Study type

Interventional

Funder types

Other

Identifiers

NCT01067690

CKS/IND-CX/05

Details and patient eligibility

About

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

Full 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.

Enrollment

25 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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