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131I-L19SIP Radioimmunotherapy (RIT) in Combination With External Beam Radiation in Patients With Multiple Brain Metastases From Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Philogen S.p.A.
ClinicalTrials.gov Identifier:
NCT01125085
First received: May 12, 2010
Last updated: February 24, 2014
Last verified: January 2014
  Purpose

The aim of this Proof of Concept study is to determine the therapeutic potential of the L19SIP antibody, labeled with the radionuclide 131I in combination with external beam radiation, for the treatment of patients with multiple brain metastases following the promising results with this agent in previous clinical studies.

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 in most aggressive types of cancer. The presented study follows a Phase I and a subsequent Phase I/II dose finding and efficacy study with the same agent in patients with a variety of cancers where 131I-L19SIP had shown an excellent tolerability and therapeutic benefit for some patients enrolled in the study.


Condition Intervention Phase
Brain Metastases From Solid Tumors
Radiation: 131I-L19SIP Radioimmunotherapy (RIT) in Combination With Whole Brain Radiation Therapy (WBRT)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective Non-randomized Study of 131I-L19SIP Radioimmunotherapy (RIT) in Combination With Whole Brain Radiation Therapy (WBRT) in Patients With Multiple Brain Metastases From Solid Tumors

Resource links provided by NLM:


Further study details as provided by Philogen S.p.A.:

Primary Outcome Measures:
  • Uptake of 131I-L19SIP or 124I-L19SIP [ Time Frame: 2 days ] [ Designated as safety issue: No ]
    Selective uptake of 131I-L19SIP or 124I-L19SIP in brain lesions

  • Safety of combined administration of 131I-L19SIP and whole brain radiation therapy (WBRT) [ Time Frame: 13 months ] [ Designated as safety issue: Yes ]
    Safety will be assessed through physical examinations, vital signs, laboratory tests (including serum chemistries, hematology parameters) and the recording of adverse events. Treatment emergent adverse events will be summarized by CTCAE version 3 (and if possible by the RTOG/EORTG scale) and worse grade for all treated patients. Laboratory values and change in vital signs will be summarized.


Secondary Outcome Measures:
  • Overall response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Intracranial, extra cranial and overall response

  • Overall survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Clinical performance index in terms of Graded Prognostic Assessment (GPA) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    GPA score will be assessed at the screening visit, during treatment and follow-up.


Enrollment: 32
Study Start Date: October 2009
Study Completion Date: June 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
131I-L19SIP RIT in Combination with WBRT
131I-L19SIP Radioimmunotherapy (RIT) in Combination With Whole Brain Radiation Therapy (WBRT)
Radiation: 131I-L19SIP Radioimmunotherapy (RIT) in Combination With Whole Brain Radiation Therapy (WBRT)
  • Patients will be treated with WBRT administering a total dosage of 30 Gy in fractions of 3 Gy
  • Dosimetric evaluation with 131I-L19SIP or 124I-L19SIP will be performed to assess eligibility for RIT.
  • Patients eligible for RIT will receive a therapeutic dose of 131I-L19SIP.
  • Total treatment duration is up to 4 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 6.3.1 Inclusion Criteria for Dosimetric Study Part (diagnostic 131I-L19SIP or 124I-L19SIP) and therapeutic study part
  • Unresectable multiple brain metastasis from histologically or cytologically confirmed solid tumors. In exceptional cases also patients with a single brain metastasis if not amenable for surgical treatment might be included.
  • Males or females, age > 18 years
  • Measurable disease defined as at least one metastatic brain lesion that can be accurately and serially measured by the modified RECIST criteria (version 1.1)
  • Prior therapy for metastatic disease allowed
  • RPA Class II
  • Life expectancy of at least 12 weeks
  • Serum creatinine < 1.5 x ULN
  • All toxic effects of prior therapy must have resolved to ≤ Grade 1 unless otherwise specified above
  • Negative serum pregnancy test (for women of child-bearing potential only) at screening
  • If of childbearing potential, agreement to use highly effective contraceptive methods (e.g., established use of oral, injected or implanted hormonal methods, placement of intrauterine device or intrauterine system, use of condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization or true abstinence) beginning at the screening visit and continuing until 3 months following last treatment with study drug.
  • In case of treated males (including men who have had vasectomies) who have a partner who is pregnant or of child-bearing potential, agreement to use condoms beginning at the screening visit and continuing until 3 months following last treatment with study drug.
  • Patients with microhaemorrhage can be included if the microhaemorrhage does not appear to significantly contribute to symptoms caused by the particular brain lesion and if the microhaemorrhage does not appear to significantly contribute to a possible mass effect of the brain lesion in question.

Additional Inclusion Criteria for Therapeutic Study Part

  • Absolute neutrophil count > 1.0 x 109/L, hemoglobin > 8.0 g/dL (packed red cell transfusions allowed), and platelets > 100 x 109/L
  • Total bilirubin ≤ 30 µmol/L (or ≤ 2.0 mg/dL). For patients with liver involvement with tumor total bilirubin ≤ 45 µmol/L (or ≤ 3.0 mg/dL).
  • ALT and AST ≤ 2.5 x the upper limit of normal (10 x ULN for patients with hepatic involvement with tumor

Exclusion Criteria:

  • Primary ocular melanoma
  • Patients with brain metastasis amenable for surgical excision or stereotactic irradiation (radiosurgery)
  • Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (TA, Tis & Ti) or any cancer curatively treated < 5 years prior to study entry
  • Patients with history of whole brain irradiation
  • History of HIV infection or infectious hepatitis B or C
  • Presence of active infections (e.g. requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.
  • Inadequately controlled cardiac arrhythmias including atrial fibrillation
  • Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria)
  • Uncontrolled hypertension
  • Ischemic peripheral vascular disease (Grade IIb-IV)
  • Severe diabetic retinopathy
  • Active autoimmune disease
  • History of organ allograft or stem cell transplantation
  • Recovery from major trauma including surgery within 4 weeks prior to administration of study treatment
  • Pregnant woman
  • Breast feeding female
  • Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before administration of study treatment
  • Growth factors or immunomodulatory agents within 7 days of the administration of study treatment
  • Patients in need of systemic treatment associated with a moderate or significant potential of hematotoxicity for rapidly progressive systemic disease during study treatment and up to 4 weeks after injection of therapeutic 131I-L19SIP.
  • Hyperthyroidism or autonomous thyroid nodule
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01125085

Locations
Italy
Irccs Centro Di Riferimento Oncologico (Cro) - Aviano
Aviano, Italy
Ospedali Riuniti Di Bergamo
Bergamo, Italy
Azienda Ospedaliero UNIVERSITARIA CAREGGI DI FIRENZE
Firenze, Italy
ASUR Zona Territoriale 9, Medicina Nucleare Ospedale di Macerata
Macerata, 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
Irccs Istituto Clinico Humanitas
Rozzano (mi), Italy
Irccs Ospedale Casa Sollievo Della Sofferenza - San Giovanni Rotondo
San Giovanni Rotondo (FG), Italy
United Kingdom
Barts and the London NHS Trust Hospital
London, United Kingdom
UCLH, Department of Cancer Medicine, London
London, United Kingdom
Sponsors and Collaborators
Philogen S.p.A.
Investigators
Principal Investigator: Secondo Lastoria, Dr ISTITUTO NAZIONALE PER LO STUDIO E LA CURA DEI TUMORI FONDAZIONE GIOVANNI PASCALE DI NAPOLI
Principal Investigator: Paul Mullholand, Dr UCLH, Department of Cancer Medicine, London (UK)
  More Information

No publications provided

Responsible Party: Philogen S.p.A.
ClinicalTrials.gov Identifier: NCT01125085     History of Changes
Other Study ID Numbers: PH-L19SIPI131-01/09, 2009-013002-13
Study First Received: May 12, 2010
Last Updated: February 24, 2014
Health Authority: Italy: Ethics Committee
Germany: Paul-Ehrlich-Institut
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Philogen S.p.A.:
I131
L19
antibody
monoclonal
multiple brain metastasis
tumor targeting
radioimmunotherapy
Patients with brain metastases of solid tumors (>1), who are not amenable for surgical excision or stereotactic radiosurgery.

Additional relevant MeSH terms:
Brain Neoplasms
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Brain Diseases
Central Nervous System Diseases
Central Nervous System Neoplasms
Neoplasms by Site
Neoplastic Processes
Nervous System Diseases
Nervous System Neoplasms
Pathologic Processes

ClinicalTrials.gov processed this record on November 24, 2014