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A Phase II Trial With the HIV Protease Inhibitor Indinavir for the Treatment of Classical Kaposi's Sarcoma

Phase 2
18 Years
Not Enrolling
Classical Kaposi's Sarcoma

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Trial Information

A Phase II Trial With the HIV Protease Inhibitor Indinavir for the Treatment of Classical Kaposi's Sarcoma

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

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.

Inclusion Criteria:

- 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-

Exclusion Criteria:

- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Assessment of clinical response every 3 months during treatment and every 6 months during follow-up based on the recommendations of ACTG.

Principal Investigator

Barbara Ensoli, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

National AIDS Center, Istituto Superiore di Sanità, Rome, Italy


Italy: The Italian Medicines Agency

Study ID:




Start Date:

June 2003

Completion Date:

July 2007

Related Keywords:

  • Classical Kaposi's Sarcoma
  • classical kaposi's sarcoma
  • treatment
  • HIV protease inhibitor indinavir
  • Sarcoma, Kaposi
  • Sarcoma