Radioimmunotherapy With 131I-L19SIP in Patients With Cancer
The aim of this Study Protocol is to provide a basis for the clinical development of 131I-L19SIP as an anti-cancer therapeutic agent, following the promising results of a Phase I study.
Patients With Cancer
Drug: 131I-L19SIP Radioimmunotherapy (RIT)
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A PHASE I/II DOSE FINDING AND EFFICACY STUDY OF THE TUMOUR TARGETING HUMAN 131I-L19SIP MONOCLONAL ANTIBODY IN PATIENTS WITH CANCER|
- Phase I: Maximum tolerated dose (MTD) [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]Establishment of the maximum tolerated dose (MTD) and the recommended dose (RD) for the radiolabelled L19SIP monoclonal antibody.
- Phase II: Antitumour activity [ Time Frame: 1- 14 months ] [ Designated as safety issue: No ]Investigation of the antitumour activity of 131I-L19SIP at the RD, in patients with advanced cancer.
- Phase I: Study of the variation of radioactivity of 131I in whole blood, at several time intervals (Pharmacokinetics) [ Time Frame: 2 days ] [ Designated as safety issue: No ]Evaluation of the pharmacokinetics of 131IL19SIP.
- Phase II: Safety profile [ Time Frame: 30 days/ administration ] [ Designated as safety issue: Yes ]Determination of the overall safety profile of the iodinated antibody characterized by type, frequency, severity, timing and relationship to study therapy of adverse events and laboratory abnormalities in the first and following cycles in all patients receiving a therapeutic dose.
- Phase II: Overall Response Rate (ORR) [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]Evaluation of the overall Response Rate (ORR) for all patients having received a therapeutic dose.
- Phase II: Progression free survival (PFS) [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]Evaluation of the progression free survival (PFS) for all patients having received a therapeutic dose.
- Phase II: Survival rate [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]Evaluation of the survival rate at 6 and 12 months and overall survival time for all patients having received a therapeutic dose.
|Study Start Date:||November 2008|
|Study Completion Date:||May 2011|
|Primary Completion Date:||February 2011 (Final data collection date for primary outcome measure)|
Experimental: L19SIP I131
Phase I: Multicentre, open-label, two-step single-arm dose escalation study in sequential cohorts of patients with cancer.
Phase II: Prospective, open-label, single-arm, multicentre study of 131I-L19SIP, given at the RD as determined in phase I.
Drug: 131I-L19SIP Radioimmunotherapy (RIT)
Dosimetric evaluation with 131I-L19SIP will be performed to assess eligibility for Radioimmunotherapy.
Phase I: Patients eligible for Radioimmunotherapy will receive escalating doses of therapeutic 131I-L19SIP administration (intravenously) at the following dosages (expressed in mCi/m2): 111, 139 and 167.
The L19SIP antibody is a fully human antibody, capable of preferential localization around tumor blood vessels while sparing normal tissues. The formation of new blood vessels is a rare event in the adult (exception made for the female reproductive cycle), but is a pathological feature of most aggressive types of cancer. The study aims at determining the therapeutic potential of the L19SIP antibody in SIP format, labelled with the radionuclide 131I, for the treatment of patients with different cancer types. The study follows a Phase I study performed with 131I-L19SIP in over 30 patients with cancer, which has shown an excellent tolerability at radioactive doses as high as 150 mCi and therapeutic benefit for some patients enrolled in the study.
|University Hospital Pisa|
|Pisa, Tuscany, Italy, 56126|
|Irst - Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori - Meldola (Fc)|
|Irccs Ospedale Casa Sollievo Della Sofferenza - San Giovanni Rotondo|
|San Giovanni Rotondo (FG), Italy|
|University College London, UCL Cancer Institute|
|London, United Kingdom|
|Principal Investigator:||Giuliano Mariani, Prof||University Hospital Pisa, Italy|
|Principal Investigator:||Tim Meyer, Dr||University College London (UCL) Cancer Institute|