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

Primary Purpose

Kaposi's Sarcoma

Status

Completed

Phase

Phase 2

Locations

Italy

Study Type

Interventional

Intervention

Indinavir in association with Vinblastina +/- Bleomicina

About this trial

This is an interventional treatment trial for Kaposi's Sarcoma focused on measuring classical Kaposi's sarcoma, chemotherapy, indinavir, HIV protease inhibitor, Advanced classical (non HIV-associated) Kaposi's sarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy

Outcomes

Primary Outcome Measures

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

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)

Full Information

NCT ID

NCT01067690

First Posted

February 10, 2010

Last Updated

August 29, 2016

Sponsor

Barbara Ensoli, MD, PhD

1. Study Identification

Unique Protocol Identification Number

NCT01067690

Brief Title

Treatment With Indinavir and Chemotherapy for Advanced Classical 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 Type

Interventional

2. Study Status

Record Verification Date

August 2016

Overall Recruitment Status

Completed

Study Start Date

June 2008 (undefined)

Primary Completion Date

October 2015 (Actual)

Study Completion Date

June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Barbara Ensoli, MD, PhD

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Kaposi's Sarcoma

Keywords

classical Kaposi's sarcoma, chemotherapy, indinavir, HIV protease inhibitor, Advanced classical (non HIV-associated) Kaposi's sarcoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Indinavir in association with Vinblastina +/- Bleomicina

Intervention Description

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.

Primary Outcome Measure Information:

Title

Secondary Outcome Measure Information:

Title

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lucia Brambilla, MD

Organizational Affiliation

Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy

Official's Role

Principal Investigator

Facility Information:

Facility Name

Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy

City

Milan

ZIP/Postal Code

20100

Country

Italy

12. IPD Sharing Statement

Citations:

PubMed Identifier

11100885

Citation

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.

Results Reference

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PubMed Identifier

11875492

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. doi: 10.1038/nm0302-225.

Results Reference

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PubMed Identifier

12965274

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

Results Reference

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PubMed Identifier

15516959

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. doi: 10.1038/nrc1479.

Results Reference

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PubMed Identifier

19169139

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.

Results Reference

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

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