Classical Kaposi's SarcomaPhase 2NCT00362310
Treatment of Classical Non-HIV-Related Kaposi's Sarcoma With the Antiviral Drug Indinavir
A Phase 2 study testing indinavir in people with Classical Kaposi's Sarcoma, run by Istituto Superiore di Sanità at 9 sites in Italy.
Trial summary
Recent studies have described a reduced incidence or the regression of Kaposi's sarcoma (KS) in HIV-infected patients treated with the highly active anti-retroviral therapy (HAART) that contains at least one inhibitor of the HIV protease (HIV-PI) such as Indinavir. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Classical Kaposi's Sarcoma
- What is being tested?
- indinavir
- How many people
- 28 participants
- Where
- 9 sitesItaly
- Study dates
- Jun 2003to Jul 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have a documented diagnosis of classical KS
- Be HIV-negative
- Be 18 years old and over
- Have one or more of the following: a minimum of 3 measurable progressive lesions; all stages of complicated KS, i.e. showing functional impotency of the affected limbs, lymphedema, lymphorrea or pain; visceral disease; lack of response to conventional therapy (radiotherapy, chemotherapy); contraindication to conventional therapies-
Who cannot join
- Presence of life-threatening lesions or other concomitant illness, neoplasia or any other clinical condition threatening the health of the patient or his compliance to the treatment
- Inability to provide informed consent
- Concomitant treatment (within 30 days of initiating study treatment) with systemic immunomodulatory agents (e.g., glucocorticoids as immunosuppressive agents, interferons) or chemotherapy
- Pregnancy
- Impaired clinical conditions (Karnofsky's index <60
- Diabetes, history of nephrolithiasis or monolateral nephropathy
Show all 17Show fewer
- Difficulty swallowing capsules/tablets
- Any clinically significant laboratory findings obtained during screening, including:
- Alkaline phosphatase (AP) >2 fold upper limit of normal (ULN)
- Aspartate aminotransferase (AST)
- Alkaline aminotransferase (ALT)
- Gamma-glutamyl transferase (gamma-GT) or total bilirubin >3 fold the ULN
- Serum creatinine >1.2 mg/d for women and >1.4 mg/dL for men or creatinine clearance > 100 +/- 25
- Pancreatic amylase >1.5 folds ULN
- Hemoglobin <10.0 g/dL for males, <9.0 g/dL for females
- Platelet count <75.000/cubic millimeter (mm3)
- Neutrophil count <850/mm3
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Italy9 sites
Centro di Riferimento Oncologico (CRO),
Aviano
Department of Internal Medicine, University of Cagliari
Cagliari
Dermatologic Clinic, Ospedale S. Anna
Ferrara
Ospedale Maggiore, Mangiagalli e Regina Elena, IRCCS,
Milan
Ospedale Civico Benfratelli
Palermo
Department of Dermatological/Venereal Diseases and Plastic Surgery, University "La Sapienza"
Rome
Istituto Dermatologico S. Gallicano-IRCCS
Rome
Istituto Dermopatico dell'Immacolata-IRCCS (IDI)
Rome
Dermatology Clinic, University of Sassari
Sassari
About this study
Official title: A Phase II Trial With the HIV Protease Inhibitor Indinavir for the Treatment of Classical Kaposi's Sarcoma
Recent studies have described a reduced incidence or the regression of Kaposi's sarcoma (KS) in HIV-infected patients treated with the highly active anti-retroviral therapy (HAART) that contains at least one inhibitor of the HIV protease (HIV-PI) such as Indinavir. Experimental studies have shown that part of the anti-KS actions of HIV-PI are not related to their antiretroviral actions, but, at least in part, to their capability of blocking angiogenesis and tumor growth.
This study will be conducted on HIV-negative (classical) KS patients to prove that Indinavir has anti-angiogenic and anti-KS effects in humans independently of its antiretroviral activity.
Read the detailed description
Kaposi's sarcoma (KS) is a rare vascular tumor affecting elderly individuals from Mediterranean countries (CKS), post transplant patients and, with increased incidence and aggressiveness, HIV-infected individuals (AIDS-KS). No definitive cure has been established for KS and all conventional therapies result in low response rate, high toxicity and tumor relapse.
Antiretroviral therapies including a HIV protease inhibitor (HIV-PI) have reduced AIDS-KS incidence and induce KS regression in treated patients. This cannot be explained solely with drug-mediated HIV suppression and immune reconstitution. We have shown that HIV-PI such as Indinavir or Saquinavir block KS-like lesions in mice by inhibiting angiogenesis and tumor cell invasion through a blockade of matrix metalloprotease 2 (MMP2) proteolytic activation.
Based on these data, a proof-of-concept clinical study on HIV-negative (classic) KS (C-KS) patients was planned to prove that Indinavir has anti-angiogenic and anti-KS effects in humans independently of its antiretroviral activity.
Recent concepts in the evaluation of non cytotoxic anti-cancer drugs such as anti-angiogenic agents suggest novel criteria for the design of clinical studies due to the specific mechanism of action of these drugs. In particular, the use of the conventional evaluation criteria based on cytotoxic actions may mislead the interpretation of the therapeutic efficacy of non cytotoxic agents. The study was therefore designed to compare the clinical response to Indinavir in early-stage vs. late-stage KS and by relating it to key biological endpoints and plasmatic drug concentrations. This was also motivated by the rareness of C-KS and by ethical reasons which prevented the inclusion of a control group.
Patients will be treated per os with 800 mg x 2/daily of Indinavir for 12 months. Follow-up will be one year.
Primary objectives:
Evaluation of the tumor response rate (complete response, partial response, improved disease and stable disease) to indinavir in the treatment of mild or severe classical KS patients; Evaluation of the duration of response in indinavir-treated patients.
Secondary objectives:
Evaluation of Indinavir safety in classical KS population; Determination of the pharmacokinetic profile of Indinavir; Evaluation of key Kaposi's sarcoma biological endpoints including markers of angiogenesis and tumor invasion, Th1 and Th2 polarization of the immune response, immunoactivation, and immune responses to HHV8, herpesviruses and common pathogens.
- Conditions
- Classical Kaposi's Sarcoma
- Being tested
- indinavir
- Keywords
- classical kaposi's sarcoma, treatment, HIV protease inhibitor indinavir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
indinavirDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of clinical response every 3 months during treatment and every 6 months during follow-up based on the recommendations of ACTG.
Secondary outcomes (1)
Monthly evaluation of toxicity and of biological endpoints every 3 months and their correlation with drug plasma levels
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2006 (estimated)
- Study startJun 2003
- Study completionJul 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Classical Kaposi's SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants
Sponsor and investigators
- Lead sponsor
- Istituto Superiore di Sanità
- Sponsor type
- University, hospital or other
- Investigators
- Barbara Ensoli, MD, PhD, Study chair, National AIDS Center, Istituto Superiore di Sanità, Rome, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00362310
- Sponsor's protocol ID
- CKS/IND/02
- Status last verified
- Apr 2008
- First submitted
- 9 Aug 2006
- Last updated
- 14 Apr 2008
- Results posted
- No
Publications
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.
PubMed 15516959Sgadari 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.
PubMed 11875492
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial With the HIV Protease Inhibitor Indinavir for the Treatment of Classical Kaposi's Sarcoma
- ClinicalTrials.gov ID
- NCT00362310
- Acronym / sponsor ID
- CKS/IND/02
- Conditions
- Classical Kaposi's Sarcoma
- Keywords
- classical kaposi's sarcoma, treatment, HIV protease inhibitor indinavir
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants
- Lead sponsor
- Istituto Superiore di SanitàUniversity, hospital or other
- Study start
- Jun 2003
- Study completion
- Jul 2007
- First posted
- 10 Aug 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Recent studies have described a reduced incidence or the regression of Kaposi's sarcoma (KS) in HIV-infected patients treated with the highly active anti-retroviral therapy (HAART) that contains at least one inhibitor of the HIV protease (HIV-PI) such as Indinavir. Experimental studies have shown that part of the anti-KS actions of HIV-PI are not related to their antiretroviral actions, but, at least in part, to their capability of blocking angiogenesis and tumor growth.
This study will be conducted on HIV-negative (classical) KS patients to prove that Indinavir has anti-angiogenic and anti-KS effects in humans independently of its antiretroviral activity.
Detailed description
Kaposi's sarcoma (KS) is a rare vascular tumor affecting elderly individuals from Mediterranean countries (CKS), post transplant patients and, with increased incidence and aggressiveness, HIV-infected individuals (AIDS-KS). No definitive cure has been established for KS and all conventional therapies result in low response rate, high toxicity and tumor relapse.
Antiretroviral therapies including a HIV protease inhibitor (HIV-PI) have reduced AIDS-KS incidence and induce KS regression in treated patients. This cannot be explained solely with drug-mediated HIV suppression and immune reconstitution. We have shown that HIV-PI such as Indinavir or Saquinavir block KS-like lesions in mice by inhibiting angiogenesis and tumor cell invasion through a blockade of matrix metalloprotease 2 (MMP2) proteolytic activation.
Based on these data, a proof-of-concept clinical study on HIV-negative (classic) KS (C-KS) patients was planned to prove that Indinavir has anti-angiogenic and anti-KS effects in humans independently of its antiretroviral activity.
Recent concepts in the evaluation of non cytotoxic anti-cancer drugs such as anti-angiogenic agents suggest novel criteria for the design of clinical studies due to the specific mechanism of action of these drugs. In particular, the use of the conventional evaluation criteria based on cytotoxic actions may mislead the interpretation of the therapeutic efficacy of non cytotoxic agents. The study was therefore designed to compare the clinical response to Indinavir in early-stage vs. late-stage KS and by relating it to key biological endpoints and plasmatic drug concentrations. This was also motivated by the rareness of C-KS and by ethical reasons which prevented the inclusion of a control group.
Patients will be treated per os with 800 mg x 2/daily of Indinavir for 12 months. Follow-up will be one year.
Primary objectives:
Evaluation of the tumor response rate (complete response, partial response, improved disease and stable disease) to indinavir in the treatment of mild or severe classical KS patients; Evaluation of the duration of response in indinavir-treated patients.
Secondary objectives:
Evaluation of Indinavir safety in classical KS population; Determination of the pharmacokinetic profile of Indinavir; Evaluation of key Kaposi's sarcoma biological endpoints including markers of angiogenesis and tumor invasion, Th1 and Th2 polarization of the immune response, immunoactivation, and immune responses to HHV8, herpesviruses and common pathogens.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Have a documented diagnosis of classical KS
- Be HIV-negative
- Be 18 years old and over
- Have one or more of the following: a minimum of 3 measurable progressive lesions; all stages of complicated KS, i.e. showing functional impotency of the affected limbs, lymphedema, lymphorrea or pain; visceral disease; lack of response to conventional therapy (radiotherapy, chemotherapy); contraindication to conventional therapies-
Key exclusion criteria (17 listed)
- Presence of life-threatening lesions or other concomitant illness, neoplasia or any other clinical condition threatening the health of the patient or his compliance to the treatment
- Inability to provide informed consent
- Concomitant treatment (within 30 days of initiating study treatment) with systemic immunomodulatory agents (e.g., glucocorticoids as immunosuppressive agents, interferons) or chemotherapy
- Pregnancy
- Impaired clinical conditions (Karnofsky's index <60
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| indinavir | Drug | – |
Primary outcome
Assessment of clinical response every 3 months during treatment and every 6 months during follow-up based on the recommendations of ACTG.
1 secondary outcome
Monthly evaluation of toxicity and of biological endpoints every 3 months and their correlation with drug plasma levels
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2008.
- Background: PubMed 15516959Monini 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.
- Background: PubMed 11875492Sgadari 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Barbara Ensoli, MD, PhD study chair
National AIDS Center, Istituto Superiore di Sanità, Rome, Italy
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing indinavir in people with Classical Kaposi's Sarcoma, run by Istituto Superiore di Sanità at 9 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Apr 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of clinical response every 3 months during treatment and every 6 months during follow-up based on the recommendations of ACTG.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00362310, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2008.