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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2010 by Istituto Superiore di Sanita.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Istituto Superiore di Sanita
ClinicalTrials.gov Identifier:
NCT01067690
First received: February 10, 2010
Last updated: NA
Last verified: February 2010
History: No changes posted
  Purpose

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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Istituto Superiore di Sanita:

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. [ Designated as safety issue: No ]

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) [ Designated as safety issue: Yes ]

Estimated Enrollment: 25
Study Start Date: June 2008
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.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01067690

Contacts
Contact: Barbara Ensoli, MD, PhD +39-06-4990 ext 3209 barbara.ensoli@iss.it
Contact: Cecilia Sgadari, MD +39-06-4990 ext 2511 cecilia.sgadari@iss.it

Locations
Italy
Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy Recruiting
Milan, Italy, 20100
Contact: Lucia Brambilla, MD    +39-02-55035115    luciabrambilla1@virgilio.it   
Contact: Biancamaria Scoppio, MD    +39-02-55035115    marinellascoppio@tiscali.it   
Principal Investigator: Lucia Brambilla, MD         
Sponsors and Collaborators
Istituto Superiore di Sanita
Investigators
Principal Investigator: Lucia Brambilla, MD Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy
  More Information

Additional Information:
Publications:
Responsible Party: Dr. Barbara Ensoli (Principal Investigator); Director, National AIDS Center, National AIDS Center, Istituto Superiore di Sanità, Rome, Italy
ClinicalTrials.gov Identifier: NCT01067690     History of Changes
Other Study ID Numbers: CKS/IND-CX/05
Study First Received: February 10, 2010
Last Updated: February 10, 2010
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Istituto Superiore di Sanita:
classical Kaposi's sarcoma
chemotherapy
indinavir
HIV protease inhibitor
Advanced classical (non HIV-associated) Kaposi's sarcoma

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

ClinicalTrials.gov processed this record on April 22, 2014