Kaposi's SarcomaPhase 2NCT01067690
Treatment With Indinavir and Chemotherapy for Advanced Classical Kaposi's Sarcoma
A Phase 2 study testing Indinavir in association with Vinblastina +/- Bleomicina in people with Kaposi's Sarcoma, run by Barbara Ensoli, MD, PhD at 1 site in Italy.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kaposi's Sarcoma
- What is being tested?
- Indinavir in association with Vinblastina +/- Bleomicina
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 25 participants
- Where
- 1 siteItaly
- Study dates
- Jun 2008to Jun 2016
- 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
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site
Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy
Milan, Italy, 20100
About this study
Official title: Phase II Trial for the Treatment of Advanced Classical Kaposi's Sarcoma With the HIV Protease Inhibitor Indinavir in Combination With Chemotherapy
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
Read the 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.
- Conditions
- Kaposi's Sarcoma
- Being tested
- Indinavir in association with Vinblastina +/- Bleomicina
- Keywords
- classical Kaposi's sarcoma, chemotherapy, indinavir, HIV protease inhibitor, Advanced classical (non HIV-associated) Kaposi's sarcoma
- Medical subject headings
- Sarcoma, Kaposi
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Indinavir in association with Vinblastina +/- BleomicinaDrug
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
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 outcomes (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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2010 (estimated)
- Study startJun 2008
- Primary completionOct 2015
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barbara Ensoli, MD, PhD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Barbara Ensoli, MD, PhD, Istituto Superiore di Sanità
- Investigators
- Lucia Brambilla, MD, Principal investigator, Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01067690
- Sponsor's protocol ID
- CKS/IND-CX/05
- Status last verified
- Aug 2016
- First submitted
- 10 Feb 2010
- Last updated
- 30 Aug 2016
- Results posted
- No
Publications
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.
PubMed 11100885Sgadari 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 11875492Sgadari 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.
PubMed 12965274Monini 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 15516959Monini 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.
PubMed 19169139
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial for the Treatment of Advanced Classical Kaposi's Sarcoma With the HIV Protease Inhibitor Indinavir in Combination With Chemotherapy
- ClinicalTrials.gov ID
- NCT01067690
- Acronym / sponsor ID
- CKS/IND-CX/05
- Conditions
- Kaposi's Sarcoma
- Keywords
- classical Kaposi's sarcoma, chemotherapy, indinavir, HIV protease inhibitor, Advanced classical (non HIV-associated) Kaposi's sarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Barbara Ensoli, MD, PhDUniversity, hospital or other
- Study start
- Jun 2008
- Primary completion
- Oct 2015 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 11 Feb 2010 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- 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 (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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
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 in association with Vinblastina +/- BleomicinaTreatment 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. | Drug | – |
Primary outcome
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.
1 secondary outcome
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)
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 30 Aug 2016.
- Background: PubMed 11100885Ensoli 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.
- 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.
- Background: PubMed 12965274Sgadari 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.
- 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 19169139Monini 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.
Related trials for Kaposi's Sarcoma
Recruiting
AYAHIV Role-based Responsibilities for Oncology-focused Workforce (ARROW)
Cervical Cancer, Kaposi Sarcoma
RecruitingObservational study
Natural History Study of Kaposi Sarcoma
Kaposi Sarcoma, HIV
Active, not recruitingPhase 2
Trial of Ixazomib for Kaposi Sarcoma
Kaposi Sarcoma, Skin
Active, not recruitingPhase 1
Pomalidomide in Combination With Liposomal Doxorubicin in People With Advanced or Refractory Kaposi Sarcoma
Kaposi Sarcoma
Active, not recruitingPhase 2
Virotherapy and Natural History Study of KHSV-Associated Multricentric Castleman s Disease With Correlates of Disease Activity
Lymphoproliferative Disorder, HHV-8
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.
Lucia Brambilla, MD principal investigator
Dermatologic Unit, Ospedale Maggiore Policlinico, Milan, Italy
1 site 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 association with Vinblastina +/- Bleomicina in people with Kaposi's Sarcoma, run by Barbara Ensoli, MD, PhD at 1 site 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 6 inclusion and 6 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 30 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
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.. 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 NCT01067690, which also lists 5 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 30 Aug 2016.