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

NCT ID: NCT01067690

Last Updated: 2016-08-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2016-06-30

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.

Conditions

Kaposi's Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Barbara Ensoli, MD, PhD

OTHER

Sponsor Role: lead

Responsible Party

Barbara Ensoli, MD, PhD

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Lucia Brambilla, MD

Role: PRINCIPAL_INVESTIGATOR

Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy

Locations

Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy

Milan, Italy, Italy

Countries

Italy

References

Ensoli B, Sturzl M, Monini P. Cytokine-mediated growth promotion of Kaposi's sarcoma and primary effusion lymphoma. Semin Cancer Biol. 2000 Oct;10(5):367-81. doi: 10.1006/scbi.2000.0329.

Reference Type: BACKGROUND

PMID: 11100885 (View on PubMed)

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. doi: 10.1038/nm0302-225.

Reference Type: BACKGROUND

PMID: 11875492 (View on PubMed)

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. doi: 10.1016/s1470-2045(03)01192-6.

Reference Type: BACKGROUND

PMID: 12965274 (View on PubMed)

Monini P, Sgadari C, Toschi E, Barillari G, Ensoli B. Antitumour effects of antiretroviral therapy. Nat Rev Cancer. 2004 Nov;4(11):861-75. doi: 10.1038/nrc1479.

Reference Type: BACKGROUND

PMID: 15516959 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19169139 (View on PubMed)

Other Identifiers

CKS/IND-CX/05

Identifier Type: -

Identifier Source: org_study_id