Patients With Intransit Stage III/IV MelanomaPhase 1NCT01213732
Phase 1 Dose-finding Study of L19TNFα Plus Melphalan Using Isolated Inferior Limb Perfusion (ILP) in Subjects With Intransit Stage III/IV Melanoma
A Phase 1 study testing Isolated inferior limb perfusion in people with Patients With Intransit Stage III/IV Melanoma, run by Philogen S.p.A. at 2 sites in Italy.
Trial summary
In this study the recombinant human fusion protein L19TNFα will be associated in ILP with the standard treatment with melphalan 10mg/l limb volume in subjects affected by stage III/IV limb melanoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Patients With Intransit Stage III/IV Melanoma
- What is being tested?
- Isolated inferior limb perfusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 2 sitesItaly
- Study dates
- Oct 2008to Sep 2011
- Phase
- Phase 1
- 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
- Subjects aged >18 years.
- Histologically or cytologically confirmed intransit stage III/IV melanoma of lower extremity distal to the apex of the femoral triangle
- ECOG performance status ≤ 2.
- Subjects must have at least one unidimensional clinically measurable lesion as defined by RECIST criteria (see Section 8). This lesion must not have been irradiated within four weeks during previous treatments.
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, and haemoglobin (Hb) ≥ 9.5 g/dl.
- All acute adverse effects (excluding alopecia) of any prior therapy (including surgery, radiation therapy, chemotherapy) must have been resolved to ≤ Grade 1, except elevated liver transaminases judged to be associated with tumor infiltration (see below) (graded according to National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events, version 3.0 [CTCAE, v.3.0].
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- Alkaline phosphatase (AP), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN), and total bilirubin ≤ 2.0 mg/dL unless liver involvement by the tumor, in which case the transaminase levels up to 5 x ULN are allowed.
- Creatinine ≤ 1.5 ULN or 24 h creatinine clearance ≥ 60 mL/min.
- Testing negative for acute or chronic infection with hepatitis B or C virus, or human immunodeficiency virus 1 or 2.
- Negative pregnancy test for females of childbearing potential at the screening visit.
- Commitment from subject to practice medically appropriate/acceptable method of birth control (e.g., hormonal, condoms or other adequate barrier controls, intrauterine contraceptive device, or sterilization) beginning at the screening visit and continuing until 3 months following the treatment with study drug
- Able to provide written Informed Consent
- Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
Who cannot join
- Breastfeeding women
- Presence of active infections (e.g. requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the Investigator, would place the subject at undue risk or interfere with the study.
- Active autoimmune disease.
- Cardiac disease as manifested by any of the following:
- > Grade II heart failure, graded per New York Heart Association (NYHA) criteria.
- Unstable angina pectoris
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- Acute or subacute coronary syndromes, including myocardial infarction, occurring with 1 year prior to study treatment
- Arrhythmia needing continuous treatment
- Ejection fraction less than the institutional lower limit of normal as assessed by multigated radionuclide angiography (MUGA) scan or echocardiogram
- Uncontrolled hypertension.
- History of claudication or Ischemic peripheral vascular disease (Grade IIb-IV).
- Chronic obstructive pulmonary disease or other chronic pulmonary disease with PFTs less than 50% predicted for age.
- Symptomatic cerebrovascular disease.
- Active peptic ulcer disease.
- Concurrent infection of HIV.
- Severe diabetic retinopathy.
- Major surgery or trauma within 4 weeks prior to start of study treatment.
- Hypersensitivity to melphalan or TNFα or other intravenously administered human proteins/peptides/antibodies.
- Chemotherapy, radiation therapy or therapy with an investigational agent within 4 weeks prior to start of study treatment.
- Any regional therapy to the affected extremity within 2 months prior to start of study treatment.
- 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 prior to the administration of study treatment.
- Subject requires or is taking corticosteroids or other immunosuppressant drugs on a long-term basis. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criterion.
- Participation in another interventional clinical trial during participation in this trial.
- Any conditions that in the opinion of the Investigator could hamper compliance with the study protocol.
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Azienda Ospedaliera Universitaria San Martino
Genova
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan
About this study
Official title: Phase 1 Dose-finding Study of Tumor-targeting Human Monoclonal Antibody-cytokine Fusion Protein L19TNFα Plus Melphalan Using Isolated Inferior Limb Perfusion in Patients With In-transit Stage III/IV Melanoma.
In this study the recombinant human fusion protein L19TNFα will be associated in ILP with the standard treatment with melphalan 10mg/l limb volume in subjects affected by stage III/IV limb melanoma.
The recombinant human fusion protein L19TNFα was created with the intention to target TNFα directly to tumor tissues with the result in high and sustained intralesional bioactive TNFα concentrations.
- Being tested
- Isolated inferior limb perfusion
- Keywords
- L19, antibody, monoclonal, tumor targeting, TNFa, ILP, melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isolated inferior limb perfusionOther
Single Melphalan bolus perfused for 60 min after 30 min of L19TNFα bolus. Intra-arterial (IA) infusion via bolus at 39˚C to 40˚C (mild hyperthermia).
| Study group | Role | What they receive |
|---|---|---|
| L19TNFα plus melphalan | Experimental | Subjects will be sequentially assigned to one of 2 dose levels of L19TNFα: 325 µg or 650 µg. All subjects will receive a single dose of L19TNFα and Melfalan (10mg/ L Limb volume). Receives: Other: Isolated inferior limb perfusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability
The safety and tolerability profile of L19TNFα/melphalan combination treatment in the ILP setting will be determined.
Measured: 6 weeks
Recommended dose (RD)
The recommended dose (RD) of L19TNFα when given in combination with melphalan in the ILP setting for subjects with limb stage III/IV melanoma will be determined.
Measured: 29 days
Secondary outcomes (5)
Objective response rate
Objective response rate of L19TNFα plus melphalan.
Measured: 10 weeks
Antitumor activity
Antitumor activity of L19TNFα plus melphalan (resection of residual tumor after 4- 6 weeks and histopathological response rate).
Measured: 4- 6 weeks
Pharmacokinetic
Pharmacokinetic profile of L19TNFα when given with melphalan
Measured: 10 days
Human anti-fusion protein antibody
Assessment of possible induction of human anti-fusion protein antibody [HAFA] formation
Measured: 6 weeks
5-hydroxyindoleacetic acid
Assessment of plasma profile of 5-hydroxyindoleacetic acid (5-HIAA), a surrogate marker of vascular damage and tumor response.
Measured: 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2010 (estimated)
- Study startOct 2008
- Primary completionMar 2011
- Study completionSep 2011
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 Patients With Intransit Stage III/IV MelanomaStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Philogen S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- InnoPharma Inc., Eudax S.r.l.
- Responsible party
- Sponsor
- Investigators
- Franco De Cian, Prof, Principal investigator, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01213732
- Sponsor's protocol ID
- PH-L19TNFαILP-01-08
- Status last verified
- Sep 2011
- First submitted
- 1 Oct 2010
- Last updated
- 15 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Papadia F, Basso V, Patuzzo R, Maurichi A, Di Florio A, Zardi L, Ventura E, Gonzalez-Iglesias R, Lovato V, Giovannoni L, Tasciotti A, Neri D, Santinami M, Menssen HD, De Cian F. Isolated limb perfusion with the tumor-targeting human monoclonal antibody-cytokine fusion protein L19-TNF plus melphalan and mild hyperthermia in patients with locally advanced extremity melanoma. J Surg Oncol. 2013 Feb;107(2):173-9. doi: 10.1002/jso.23168. Epub 2012 Jun 4.
PubMed 22674435
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Dose-finding Study of Tumor-targeting Human Monoclonal Antibody-cytokine Fusion Protein L19TNFα Plus Melphalan Using Isolated Inferior Limb Perfusion in Patients With In-transit Stage III/IV Melanoma.
- ClinicalTrials.gov ID
- NCT01213732
- Acronym / sponsor ID
- PH-L19TNFαILP-01-08
- Keywords
- L19, antibody, monoclonal, tumor targeting, TNFa, ILP, melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Philogen S.p.A.Industry (pharma, biotech, devices)
- Collaborators
- InnoPharma Inc., Eudax S.r.l.
- Study start
- Oct 2008
- Primary completion
- Mar 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 4 Oct 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.
In this study the recombinant human fusion protein L19TNFα will be associated in ILP with the standard treatment with melphalan 10mg/l limb volume in subjects affected by stage III/IV limb melanoma.
The recombinant human fusion protein L19TNFα was created with the intention to target TNFα directly to tumor tissues with the result in high and sustained intralesional bioactive TNFα concentrations.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| L19TNFα plus melphalan | Experimental | Other: Isolated inferior limb perfusionSubjects will be sequentially assigned to one of 2 dose levels of L19TNFα: 325 µg or 650 µg. All subjects will receive a single dose of L19TNFα and Melfalan (10mg/ L Limb volume). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Subjects aged >18 years.
- Histologically or cytologically confirmed intransit stage III/IV melanoma of lower extremity distal to the apex of the femoral triangle
- ECOG performance status ≤ 2.
- Subjects must have at least one unidimensional clinically measurable lesion as defined by RECIST criteria (see Section 8). This lesion must not have been irradiated within four weeks during previous treatments.
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, and haemoglobin (Hb) ≥ 9.5 g/dl.
Key exclusion criteria (25 listed)
- Breastfeeding women
- Presence of active infections (e.g. requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the Investigator, would place the subject at undue risk or interfere with the study.
- Active autoimmune disease.
- Cardiac disease as manifested by any of the following:
- Uncontrolled hypertension.
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 |
|---|---|---|
| Isolated inferior limb perfusionSingle Melphalan bolus perfused for 60 min after 30 min of L19TNFα bolus. Intra-arterial (IA) infusion via bolus at 39˚C to 40˚C (mild hyperthermia). | Other | L19TNFα plus melphalan |
Primary outcome
Safety and Tolerability
Time frame: 6 weeks
The safety and tolerability profile of L19TNFα/melphalan combination treatment in the ILP setting will be determined.
Recommended dose (RD)
Time frame: 29 days
The recommended dose (RD) of L19TNFα when given in combination with melphalan in the ILP setting for subjects with limb stage III/IV melanoma will be determined.
5 secondary outcomes
Objective response rate
Time frame: 10 weeks
Antitumor activity
Time frame: 4- 6 weeks
Pharmacokinetic
Time frame: 10 days
Human anti-fusion protein antibody
Time frame: 6 weeks
5-hydroxyindoleacetic acid
Time frame: 10 days
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 15 Apr 2022.
- Derived from this study: PubMed 22674435Papadia F, Basso V, Patuzzo R, Maurichi A, Di Florio A, Zardi L, Ventura E, Gonzalez-Iglesias R, Lovato V, Giovannoni L, Tasciotti A, Neri D, Santinami M, Menssen HD, De Cian F. Isolated limb perfusion with the tumor-targeting human monoclonal antibody-cytokine fusion protein L19-TNF plus melphalan and mild hyperthermia in patients with locally advanced extremity melanoma. J Surg Oncol. 2013 Feb;107(2):173-9. doi: 10.1002/jso.23168. Epub 2012 Jun 4.
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.
Franco De Cian, Prof principal investigator
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Isolated inferior limb perfusion in people with Patients With Intransit Stage III/IV Melanoma, run by Philogen S.p.A. at 2 sites in Italy.
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 13 inclusion and 25 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 15 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Safety and Tolerability (time frame: 6 weeks). 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 NCT01213732, 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 15 Apr 2022.