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

Kaposi's Sarcoma Clinical Trial

Official title:

Phase II Trial for the Treatment of Advanced Classical Kaposi's Sarcoma With the HIV Protease Inhibitor Indinavir in Combination With Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01067690
• Other study ID #: CKS/IND-CX/05
• Status: Completed
• Phase: Phase 2
• First received: February 10, 2010
• Last updated: August 29, 2016
• Start date: June 2008
• Est. completion date: June 2016

Study information

• Verified date: August 2016
• Source: Istituto Superiore di Sanità
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: June 2016
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kaposi's Sarcoma
• Sarcoma
• Sarcoma, Kaposi

Intervention

Drug:
• Indinavir in association with Vinblastina +/- Bleomicina
Treatment consists in an induction phase where daily Indinavir (800 mg x 2/die, orally) will be combined together with systemic Vinblastine (10 mg intravenously) +/- Bleomycin (15 mg intramuscularly) in cycles administered every 3 weeks. As maximal response will occur, patients will undergo 2 additional Vinblastine +/- Bleomycin (consolidation) cycles upon continuous treatment with Indinavir. This will be followed by a maintenance phase with Indinavir alone (800 mg x 3/die, orally) in responder patients.

Locations

Country	Name	City	State
Italy	Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Barbara Ensoli, MD, PhD

Country where clinical trial is conducted

Italy, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.			No
Secondary	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)			Yes

External Links

•   Principal Investigator (National AIDS Center, ISS) homepage