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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01067690
Recruitment Status : Completed
First Posted : February 11, 2010
Last Update Posted : August 30, 2016
Information provided by (Responsible Party):
Barbara Ensoli, MD, PhD, Istituto Superiore di Sanità

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

Condition or disease Intervention/treatment Phase
Kaposi's Sarcoma Drug: Indinavir in association with Vinblastina +/- Bleomicina Phase 2

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : June 2008
Actual Primary Completion Date : October 2015
Actual Study Completion Date : June 2016

Intervention Details:
  • 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.

Primary Outcome Measures :
  1. 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 :
  1. 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)

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01067690

Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy
Milan, Italy, 20100
Sponsors and Collaborators
Barbara Ensoli, MD, PhD
Principal Investigator: Lucia Brambilla, MD Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy

Additional Information:
Responsible Party: Barbara Ensoli, MD, PhD, MD, Istituto Superiore di Sanità Identifier: NCT01067690     History of Changes
Other Study ID Numbers: CKS/IND-CX/05
First Posted: February 11, 2010    Key Record Dates
Last Update Posted: August 30, 2016
Last Verified: August 2016

Keywords provided by Barbara Ensoli, MD, PhD, Istituto Superiore di Sanità:
classical Kaposi's sarcoma
HIV protease inhibitor
Advanced classical (non HIV-associated) Kaposi's sarcoma

Additional relevant MeSH terms:
Sarcoma, Kaposi
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Neoplasms, Vascular Tissue
Protease Inhibitors
HIV Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents