E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with advanced Kaposi sarcoma, stage III/IV |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023287 |
E.1.2 | Term | Kaposi's sarcoma classical |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary endpoint of this study is to evaluate the effects of Indinavir on the clinical response of advanced KS upon debulking therapy with Vinblastine and Bleomicin combined. In particular, the primary endpoints are: to evaluate the rate of complete responses at the end of treatment, including the maintenance phase; to evaluate the rate of complete response, partial response, improved disease, stable disease or progression observed upon the maintenance phase with Indinavir alone, considering the residual debulked tumor (after the induction phase) as the reference point. |
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E.2.2 | Secondary objectives of the trial |
The secondary endpoints of this study are: to evaluate the entity of partial responses; to determine the time to progression of the enrolled patients; to evaluate the feasibility of the association of Indinavir and chemotherapy; to evaluate the toxicity of Indinavir used in association with chemotherapy; to evaluate the pharmacokinetic profile of Indinavir in the selected patient population; to determine the most relevant biological markers of response and the markers predictive of response to therapy, including plasmatic levels of MMPs, angiogenic factors, circulating endothelial cells and immunoactivation parameters, levels of HHV8 viremia and humoral immune response. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All subjects enrolled in this study must: - have a documented diagnosis of KS; - be HIV-negative as proven by approved test [enzyme-linked immunosorbent assay (ELISA) antibody at screening]; - be classified as a stage III or IV; - be 18 years old; - have stopped every other anti-KS therapy since at least 2 weeks; - be informed of the nature of the study and have provided written informed consent. |
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E.4 | Principal exclusion criteria |
Any one or more of the following are cause for exclusion from the study: - inability to give informed consent; - other concomitant illness, neoplasia, with the exception of small non-melanoma skin cancers, or any other clinical condition threatening the health of the patient or his compliance to the treatment; - concomitant treatment (within 2 weeks of initiating study treatment) with systemic immunomodulatory agents (e.g., glucocorticoids as immunosuppressive agents, interferons) or chemotherapy; - pregnancy [confirmed by a positive urine/serum beta human chorionic gonadropin&#61472;&#61480;&#61538;HCG) test]. Patients who became pregnant during the study will be discontinued from the study; - severe restrictive bronchopneumopathies, interstitial fibrosis, chronic asthma or bronchitis; - previous total load of systemic Bleomycin >90 mg; - monolateral nephropathy or history of nephrolitiasis in the last 5 years; - any clinically significant and persistent laboratory findings obtained during screening, including: alkaline phosphatase (AP), aspartate aminotransferase (AST), alkaline aminotransferase (ALT), &#61543;-glutamyl transferase (&#61543;-GT) or total bilirubin >3 fold upper limit of normal (ULN); pancreatic amylase >1.5 folds ULN; hemoglobin <10.0 g/dL for males, <9.0 g/dL for females; platelet count <100.000/cubic millimeter (mm3); neutrophil count <1500/mm3; uricemia >6 mg/dl, proteinuria >300 mg/day loss, microscopic hematuria presents in 3 consecutive samples in the absence of urinary infection; serum creatinine >1.2 mg/d for women and >1.4 mg/dL for men or creatinine clearance > 100 + 25, Only in patients over sixty years old creatinine clearance will be calculated according to the Cochrofts formula that is for men: (140 - age of patient) x ideal weight = creatinine clearance 72 x plasmatic creatinine For women the same formula will be multiplied for 0.85. In these patients creatinine clearance must be > 50 mg/min. If creatinine clearance <50 mg/min they must be excluded from the study; - difficulty in swallowing capsules/tablets; Previous treatment with Indinavir is not an exclusion criterion. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary objectives of the trial are the evaluation of tumor response to Indinavir and assessment of time to response, duration of response and time to progression. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |