A Dose Finding and Efficacy Study of the Tumour Targeting Human 131I-F16SIP Monoclonal Antibody 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: NCT01240720
Recruitment Status : Completed
First Posted : November 15, 2010
Last Update Posted : February 25, 2014
Eudax S.r.l.
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-F16SIP as an anti-cancer therapeutic agent.

The study follows and is greatly motivated by the promising results of a Phase I/II study with a similar investigational drug developed by our Company, 131I-L19SIP, in several Italian centers.

Condition or disease Intervention/treatment Phase
Cancer Drug: 131I-F16SIP Radioimmunotherapy (RIT) Phase 1 Phase 2

Detailed Description:
The F16SIP antibody is a fully human antibody, capable of preferential localization around tumour 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 F16 antibody in SIP format,labelled with the radionuclide 131I, for the treatment of patients with different cancer types.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Dose Finding and Efficacy Study of the Tumour Targeting Human 131I-F16SIP Monoclonal Antibody in Patients With Cancer
Study Start Date : September 2008
Actual Primary Completion Date : November 2011
Actual Study Completion Date : April 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: I131-F16SIP

Phase I: Multicentre, open-label, two-step singlearm dose escalation study in sequential cohorts of patients with cancer.

Phase II: Prospective, open-label, single-arm, multicentre study of 131I-F16SIP, given at the RD of 55.5 mCi/m2, as determined in phase I.

Drug: 131I-F16SIP Radioimmunotherapy (RIT)
  • Dosimetric evaluation with 131I-F16SIP or 124I-F16SIP will be performed to assess eligibility for Radioimmunotherapy.
  • Patients eligible for Radioimmunotherapy will receive 55.5 mCi/m2 as established in the Phase I part of the study. A single dose of 5 to 10 mg of 131I-F16SIP will be administered intravenously (I.V).

Primary Outcome Measures :
  1. Phase I: Maximum tolerated Dose [ Time Frame: 4 weeks ]
    Establishment of the maximum tolerated dose (MTD), a recommended dose (RD) for the phase II part, and the safety of dosimetric and therapeutic administration of escalating dosages of the human radiolabeled antibody 131I-F16SIP.

  2. Phase II: Antitumour activity [ Time Frame: 14 months ]
    Investigation of the antitumour activity of 131I-F16SIP at the RD.

Secondary Outcome Measures :
  1. Phase I: Study of the variation of radioactivity of 131I or 124I in whole blood, at several time intervals (Pharmacokinetics) [ Time Frame: 2 days ]
    Evaluation of the pharmacokinetics of 131I-F16SIP and 124I-F16SIP.

  2. Phase II: Adverse Events as a Measure of Safety [ 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 eventual following administrations 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 and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Phase I:

    Patients with cancer, with progressive disease in pre-study period, refractory to conventional standard treatments.

    Solid Tumor: Histologically/cytologically confirmed diagnosis of cancer, preferably lung cancer, prostate cancer or 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 be confirmed by cytology/histology.

    Lymphoproliferative Diseases: Histologically/cytologically confirmed diagnosis of lymphoproliferative disease. 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 needs to be confirmed by cytology/histology.

    Phase II:

    Patients with lymphoma, breast cancer or lung cancer with progressive disease in pre-study period, refractory to conventional standard treatments, will be enrolled in the study. Presence of brain metastases at time of screening does not represent an exclusion criterion. Lesions will be evaluated according to RECIST for solid tumors or to the Revised response criteria for malignant lymphoma (Cheson BD, JCO 2007, 25, 579-58) for lymphomas.

  2. ECOG performance status grade 0 or 1.
  3. Age ≥18.
  4. Adequate haematological, liver and renal function (haemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 1.50 x 109/L; platelets ≥ 100 x 109/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.
  5. 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.
  6. Negative serum pregnancy test for females of childbearing potential within 14 days of starting treatment.
  7. 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.
  8. 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.
  9. Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
  10. Life expectancy of at least 3 months.
  11. Signed and dated informed consent.

Exclusion Criteria:

  1. Chemotherapy, radiation, hormonotherapy or immunotherapy or participation in any investigational drug study within 4 weeks of RIT treatment at the RD (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): NCT01240720

University Hospital Pisa
Pisa, Tuscany, Italy, 56126
Policlinico S. Orsola-Malpighi- Azienda Ospedaliero-Universitaria di Bologna
Bologna, Italy
ASUR Zona Territoriale 9, Medicina Nucleare Ospedale di Macerata
Macerata, Italy
Irst - Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori - Meldola (Fc)
Meldola, Italy
Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale Di Napoli
Napoli, Italy
Arcispedale Santa Maria Nuova Di Reggio Emilia
Reggio Emilia, Italy
Sponsors and Collaborators
Philogen S.p.A.
Eudax S.r.l.
Principal Investigator: Maddalena Sansovini, Dr IRST (Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori)

Responsible Party: Philogen S.p.A. Identifier: NCT01240720     History of Changes
Other Study ID Numbers: PH-F16SIPI131-06/07
First Posted: November 15, 2010    Key Record Dates
Last Update Posted: February 25, 2014
Last Verified: February 2014

Keywords provided by Philogen S.p.A.:
tumor targeting
lymphoma, breast and lung cancer
Patients with different cancer types

Additional relevant MeSH terms:
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs