Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Barbara Ensoli, MD, Istituto Superiore di Sanità
ClinicalTrials.gov Identifier:
NCT01067690
First received: February 10, 2010
Last updated: May 20, 2014
Last verified: May 2014
  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 Sanità:

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 ]

Enrollment: 25
Study Start Date: June 2008
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01067690

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

Additional Information:
Publications:
Responsible Party: Barbara Ensoli, MD, MD, Istituto Superiore di Sanità
ClinicalTrials.gov Identifier: NCT01067690     History of Changes
Other Study ID Numbers: CKS/IND-CX/05
Study First Received: February 10, 2010
Last Updated: May 20, 2014
Health Authority: Italy: The Italian Medicines Agency

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

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

ClinicalTrials.gov processed this record on November 20, 2014