Radioimmunotherapy With 131I-L19SIP in Patients With Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01242943
Recruitment Status : Terminated (With the determination of the RD and a well established understanding of the safety and tolerability profile, the main endpoints of the study have been met.)
First Posted : November 17, 2010
Last Update Posted : November 22, 2011
Information provided by (Responsible Party):
Philogen S.p.A.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Patients With Cancer Drug: 131I-L19SIP Radioimmunotherapy (RIT) Phase 1 Phase 2

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  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Study Start Date : November 2008
Actual Primary Completion Date : February 2011
Actual Study Completion Date : May 2011

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.

Primary Outcome Measures :
  1. Phase I: Maximum tolerated dose (MTD) [ Time Frame: 4 weeks ]
    Establishment of the maximum tolerated dose (MTD) and the recommended dose (RD) for the radiolabelled L19SIP monoclonal antibody.

  2. Phase II: Antitumour activity [ Time Frame: 1- 14 months ]
    Investigation of the antitumour activity of 131I-L19SIP at the RD, in patients with advanced cancer.

Secondary Outcome Measures :
  1. Phase I: Study of the variation of radioactivity of 131I in whole blood, at several time intervals (Pharmacokinetics) [ Time Frame: 2 days ]
    Evaluation of the pharmacokinetics of 131IL19SIP.

  2. Phase II: Safety profile [ Time Frame: 30 days/ administration ]
    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.

  3. Phase II: Overall Response Rate (ORR) [ Time Frame: 6 and 12 months ]
    Evaluation of the overall Response Rate (ORR) for all patients having received a therapeutic dose.

  4. Phase II: Progression free survival (PFS) [ Time Frame: 6 and 12 months ]
    Evaluation of the progression free survival (PFS) for all patients having received a therapeutic dose.

  5. Phase II: Survival rate [ Time Frame: 6 and 12 months ]
    Evaluation of the survival rate at 6 and 12 months and overall survival time for all patients having received a therapeutic dose.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01242943

University Hospital Pisa
Pisa, Tuscany, Italy, 56126
Irst - Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori - Meldola (Fc)
Meldola, Italy
Irccs Ospedale Casa Sollievo Della Sofferenza - San Giovanni Rotondo
San Giovanni Rotondo (FG), Italy
United Kingdom
University College London, UCL Cancer Institute
London, United Kingdom
Sponsors and Collaborators
Philogen S.p.A.
Principal Investigator: Giuliano Mariani, Prof University Hospital Pisa, Italy
Principal Investigator: Tim Meyer, Dr University College London (UCL) Cancer Institute

Responsible Party: Philogen S.p.A. Identifier: NCT01242943     History of Changes
Other Study ID Numbers: PH-L19SIPI131-07/07
First Posted: November 17, 2010    Key Record Dates
Last Update Posted: November 22, 2011
Last Verified: November 2011

Keywords provided by Philogen S.p.A.:
tumour targeting