Radioimmunotherapy With 131I-L19SIP in Patients With Cancer

A PHASE I/II DOSE FINDING AND EFFICACY STUDY OF THE TUMOUR TARGETING HUMAN 131I-L19SIP MONOCLONAL ANTIBODY 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.

Study Overview

• Status: Terminated
• Conditions: Patients With Cancer
• Intervention / Treatment: Drug: 131I-L19SIP Radioimmunotherapy (RIT)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Italy
  • Meldola, Italy
    • Irst - Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori - Meldola (Fc)
  • San Giovanni Rotondo (FG), Italy
    • Irccs Ospedale Casa Sollievo Della Sofferenza - San Giovanni Rotondo
  • Tuscany
    • Pisa, Tuscany, Italy, 56126
      • University Hospital Pisa
• United Kingdom
  • London, United Kingdom
    • University College London, UCL Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with cancer, with progressive disease in pre-study period, refractory to conventional standard treatments.
2. Histologically/cytologically confirmed diagnosis of cancer, preferably lung cancer, prostate cancer and colorectal cancer (CRC). At least one measurable (minimum 2.0 cm), non irradiated lesion defined according to modified RECIST criteria, i.e. whenever the measurable disease is restricted to a solitary lesion, its neoplastic nature need not to be confirmed by cytology/histology.
3. ECOG performance status grade 0 or 1.
4. Age ≥18 and ≤ 75 years.
5. Adequate haematological, liver and renal function (haemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 1.50 x 10^9/L; platelets ≥ 100 x 10^9/L, bilirubin within UNL; alkaline phosphatase≤ 2.5 x UNL; ALT, AST ≤ UNL or ≤ 2.5 x UNL in case of liver metastases; albumin ≥ 2.5 g/dL; creatinine ≤ UNL.
6. All acute toxic effects (excluding alopecia) of any prior therapy (including surgery radiation therapy, chemotherapy) must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v.3.0) Grade ≤ 1.
7. Negative serum pregnancy test for females of childbearing potential within 14 days of starting treatment.
8. If of childbearing potential, agreement to use adequate contraceptive methods (e.g. oral contraceptives, condoms, or other adequate barrier controls, intrauterine contraceptive devices, or sterilization) beginning at the screening visit and continuing until 3 months following last treatment with study drug.
9. Evidence of a personally signed and dated IEC-approved Informed Consent indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the study.
10. Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
11. Life expectancy of at least 3 months.
12. Signed and dated informed consent.

Exclusion Criteria:

1. Chemotherapy, radiation, hormonotherapy (with the exception of a gradual titration of LHRH agonists) or immunotherapy or participation in any investigational drug study within 4 weeks of study entry (6 weeks in case of prior nitroureas chemotherapy).
2. Prior radiation dose > 30% of bone marrow volume.
3. Presence of cirrhosis or active hepatitis.
4. Presence of serious cardiac (congestive heart failure, heart insufficiency > grade II NYHA, angina pectoris, myocardial infarction within one year prior to study entry, uncontrolled hypertension or arrhythmia), neurological or psychiatric disorders.
5. Presence of uncontrolled intercurrent illness or any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study.
6. Recovery from major trauma including surgery within 4 weeks of administration of study treatment.
7. Pregnancy or lactation or unwillingness to use adequate method of birth control.
8. Active infection or incomplete wound healing.
9. Known history of allergy to intravenously administered proteins / peptides / antibodies.
10. Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: Maximum tolerated dose (MTD)	Establishment of the maximum tolerated dose (MTD) and the recommended dose (RD) for the radiolabelled L19SIP monoclonal antibody.	4 weeks
Phase II: Antitumour activity	Investigation of the antitumour activity of 131I-L19SIP at the RD, in patients with advanced cancer.	1- 14 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase II: Overall Response Rate (ORR)	Evaluation of the overall Response Rate (ORR) for all patients having received a therapeutic dose.	6 and 12 months
Phase II: Progression free survival (PFS)	Evaluation of the progression free survival (PFS) for all patients having received a therapeutic dose.	6 and 12 months
Phase II: Survival rate	Evaluation of the survival rate at 6 and 12 months and overall survival time for all patients having received a therapeutic dose.	6 and 12 months
Phase I: Study of the variation of radioactivity of 131I in whole blood, at several time intervals (Pharmacokinetics)	Evaluation of the pharmacokinetics of 131IL19SIP.	2 days
Phase II: Safety profile	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.	30 days/ administration

Collaborators and Investigators

• Sponsor: Philogen S.p.A.
• Investigators: Principal Investigator: Giuliano Mariani, Prof, University Hospital Pisa, Italy; Principal Investigator: Tim Meyer, Dr, University College London (UCL) Cancer Institute

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: November 16, 2010
• First Submitted That Met QC Criteria: November 16, 2010
• First Posted (Estimate): November 17, 2010

Study Record Updates

• Last Update Posted (Estimate): November 22, 2011
• Last Update Submitted That Met QC Criteria: November 21, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: cancer; antibody; radioimmunotherapy; monoclonal; I131; L19; tumour targeting
• Other Study ID Numbers: PH-L19SIPI131-07/07