Brain Metastases From Solid TumorsPhase 2NCT01125085
131I-L19SIP Radioimmunotherapy (RIT) in Combination With External Beam Radiation in Patients With Multiple Brain Metastases From Solid Tumors
A Phase 2 study testing 131I-L19SIP Radioimmunotherapy (RIT) in Combination With Whole Brain Radiation Therapy (WBRT) in people with Brain Metastases From Solid Tumors, run by Philogen S.p.A. at 10 sites in 2 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases From Solid Tumors
- What is being tested?
- 131I-L19SIP Radioimmunotherapy (RIT) in Combination With Whole Brain Radiation Therapy (WBRT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 10 sitesin 2 countries
- Study dates
- Oct 2009to Jun 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
Italy8 sites
Irccs Centro Di Riferimento Oncologico (Cro) - Aviano
Aviano
Ospedali Riuniti Di Bergamo
Bergamo
Azienda Ospedaliero UNIVERSITARIA CAREGGI DI FIRENZE
Florence
Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale Di Napoli
Naples
ASUR Zona Territoriale 9, Medicina Nucleare Ospedale di Macerata
Province of Macerata
Arcispedale Santa Maria Nuova Di Reggio Emilia
Reggio Emilia
Irccs Istituto Clinico Humanitas
Rozzano (mi)
Irccs Ospedale Casa Sollievo Della Sofferenza - San Giovanni Rotondo
San Giovanni Rotondo (FG)
United Kingdom2 sites
Barts and the London NHS Trust Hospital
London
UCLH, Department of Cancer Medicine, London
London
About this study
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
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.
- Conditions
- Brain Metastases From Solid Tumors
- Being tested
- 131I-L19SIP Radioimmunotherapy (RIT) in Combination With Whole Brain Radiation Therapy (WBRT)
- Keywords
- 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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
131I-L19SIP Radioimmunotherapy (RIT) in Combination With Whole Brain Radiation Therapy (WBRT)Radiation
- 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
| Study group | Role | What they receive |
|---|---|---|
| 131I-L19SIP RIT in Combination with WBRT | Other | 131I-L19SIP Radioimmunotherapy (RIT) in Combination With Whole Brain Radiation Therapy (WBRT) Receives: Radiation: 131I-L19SIP Radioimmunotherapy (RIT) in Combination With Whole Brain Radiation Therapy (WBRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Uptake of 131I-L19SIP or 124I-L19SIP
Selective uptake of 131I-L19SIP or 124I-L19SIP in brain lesions
Measured: 2 days
Safety of combined administration of 131I-L19SIP and whole brain radiation therapy (WBRT)
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.
Measured: 13 months
Secondary outcomes (3)
Overall response
Intracranial, extra cranial and overall response
Measured: 12 months
Overall survival
Measured: 12 months
Clinical performance index in terms of Graded Prognostic Assessment (GPA)
GPA score will be assessed at the screening visit, during treatment and follow-up.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2010 (estimated)
- Study startOct 2009
- Primary completionOct 2012
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain Metastases From Solid TumorsStudies of the same condition, open and under way.
- More trials run by Philogen S.p.A.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Philogen S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Secondo Lastoria, Dr, Principal investigator, ISTITUTO NAZIONALE PER LO STUDIO E LA CURA DEI TUMORI FONDAZIONE GIOVANNI PASCALE DI NAPOLIPaul Mullholand, Dr, Principal investigator, UCLH, Department of Cancer Medicine, London (UK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01125085
- Sponsor's protocol ID
- PH-L19SIPI131-01/09
- Other IDs
- 2009-013002-13, 2009
- Status last verified
- Jan 2014
- First submitted
- 12 May 2010
- Last updated
- 25 Feb 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Poli GL, Bianchi C, Virotta G, Bettini A, Moretti R, Trachsel E, Elia G, Giovannoni L, Neri D, Bruno A. Radretumab radioimmunotherapy in patients with brain metastasis: a 124I-L19SIP dosimetric PET study. Cancer Immunol Res. 2013 Aug;1(2):134-43. doi: 10.1158/2326-6066.CIR-13-0007. Epub 2013 May 20.
PubMed 24777501
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01125085
- Acronym / sponsor ID
- PH-L19SIPI131-01/09
- Conditions
- Brain Metastases From Solid Tumors
- Keywords
- 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.
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Philogen S.p.A.Industry (pharma, biotech, devices)
- Study start
- Oct 2009
- Primary completion
- Oct 2012 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 18 May 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 131I-L19SIP RIT in Combination with WBRT | Other | Radiation: 131I-L19SIP Radioimmunotherapy (RIT) in Combination With Whole Brain Radiation Therapy (WBRT)131I-L19SIP Radioimmunotherapy (RIT) in Combination With Whole Brain Radiation Therapy (WBRT) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Radiation | 131I-L19SIP RIT in Combination with WBRT |
Primary outcome
Uptake of 131I-L19SIP or 124I-L19SIP
Time frame: 2 days
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
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.
3 secondary outcomes
Overall response
Time frame: 12 months
Overall survival
Time frame: 12 months
Clinical performance index in terms of Graded Prognostic Assessment (GPA)
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2014.
- Derived from this study: PubMed 24777501Poli GL, Bianchi C, Virotta G, Bettini A, Moretti R, Trachsel E, Elia G, Giovannoni L, Neri D, Bruno A. Radretumab radioimmunotherapy in patients with brain metastasis: a 124I-L19SIP dosimetric PET study. Cancer Immunol Res. 2013 Aug;1(2):134-43. doi: 10.1158/2326-6066.CIR-13-0007. Epub 2013 May 20.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Secondo Lastoria, Dr principal investigator
ISTITUTO NAZIONALE PER LO STUDIO E LA CURA DEI TUMORI FONDAZIONE GIOVANNI PASCALE DI NAPOLI
Paul Mullholand, Dr principal investigator
UCLH, Department of Cancer Medicine, London (UK)
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 131I-L19SIP Radioimmunotherapy (RIT) in Combination With Whole Brain Radiation Therapy (WBRT) in people with Brain Metastases From Solid Tumors, run by Philogen S.p.A. at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Italy, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Uptake of 131I-L19SIP or 124I-L19SIP (time frame: 2 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01125085, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2014.