AzTrials
AzTrials

Solid TumorsPhase 1/2NCT01253837

L19TNFα in Patients With Advanced Solid Tumors

A Phase 1/2 study testing L19TNFa in people with Solid Tumors and Colorectal Cancer, run by Philogen S.p.A. at 2 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The recombinant human fusion protein L19TNFα was created with the intention to overcome the systemic toxicity of TNFα by directly targeting it to tumor tissues. Tumor-targeted L19TNFα would result in high and sustained intralesional bioactive TNFα concentrations. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumors, Colorectal Cancer
What is being tested?
L19TNFa
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
2 sitesItaly
Study dates
Sep 2007to Sep 2011
Phase
Phase 1/2
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

  • Phase I: histologically or cytologically confirmed relapsed or refractory locally advanced or metastatic solid tumor of any origin, not amenable to standard therapy.
  • Phase II: histologically or cytologically confirmed relapsed or refractory locally advanced or metastatic colorectal cancer not amenable to standard therapy.
  • For both phase I and II:
  • Subjects aged ≥ 18 years.
  • ECOG performance status ≤ 2.
  • Subjects must have at least one unidimensionally measurable lesion by computed tomography as defined by RECIST criteria (see Section 8) or tumour markers parameters of disease such as PSA and CA125 for Prostate cancer and Ovarian cancer, respectively. This lesion must not have been irradiated during previous treatments.
Show all 14Show fewer
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, platelets ≥ 100 x 10^9/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 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]).
  • Alkaline phosphatase (ALP), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN), and total bilirubin ≤ 2.0 mg/gL 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 last treatment with study drug.
  • Able to provide written Informed Consent.

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.
  • Known brain metastases or signs and/or symptoms suggestive of brain metastases.
  • Known cancer of other primary origin (excluding Stage I non-melanoma skin cancer) within the prior 5 years.
  • Active autoimmune disease.
  • Cardiac disease as manifested by any of the following:
Show all 24Show fewer
  • > Grade II heart failure, graded per New York Heart Association (NYHA) criteria.
  • Unstable angina pectoris.
  • 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.
  • Ischemic peripheral vascular disease (Grade IIb-IV).
  • Severe diabetic retinopathy.
  • Major surgery or trauma within 4 weeks prior to start of study treatment.
  • Known history of allergy to TNFα or other intravenously administered human proteins/peptides/antibodies.
  • Chemotherapy, radiation therapy or therapy with an investigational agent within 4 weeks prior 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 the 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.
  • Concurrent therapy with warfarin at doses greater than 1 mg/day or equivalent doses of other coumarin derivatives.
  • Participation in another interventional clinical trial during participation in this trial.
  • Expectation that the subject will not be able to complete at least 6 weeks of therapy.
  • 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

  • A.O. UNIVERSITARIA OSPEDALI RIUNITI - OSPEDALE UMBERTO I DI ANCONA - ANCONA (Italy)

    Ancona

  • European Istitue of Oncology Milan (Italy)

    Milan

Other trials in Italy

About this study

Official title: Phase I/II Study of the Tumor-targeting Human L19TNFα Monoclonal Antibody-cytokine Fusion Protein in Patients With Advanced Solid Tumors

The recombinant human fusion protein L19TNFα was created with the intention to overcome the systemic toxicity of TNFα by directly targeting it to tumor tissues. Tumor-targeted L19TNFα would result in high and sustained intralesional bioactive TNFα concentrations.

Read the detailed description

The primary purpose of this Phase I/II study is to define a safe and potentially active treatment regimen of L19TNFα as a monotherapy and to evaluate the antitumor activity of this regimen in relapsed metastatic colorectal cancer subjects, for whom standard treatment options are exhausted. L19TNFα is an investigational drug that specifically and effectively binds to ED-B, which is abundantly expressed in cancer tissue. Accordingly, treatment should result in a high and long-lasting intratumoral accumulation of biologically active rh-TNFα. Although combined therapies of TNFα with cytotoxic drugs (e.g. melphalan) seem to be strikingly more active against sarcoma and melanoma than with TNFα alone - at least for the ILP setting it seems possible that the repeated intratumoral delivery of TNFα via L19TNFα might produce additional biologic effects, such as the induction of an immunologic antitumor response or the sustained inhibition of tumor-associated angiogenesis (Lejeune, 2006), that potentially could benefit advanced cancer subjects.

Being tested
L19TNFa
Keywords
L19, antibody, monoclonal, tumor targeting, TNFa, colorectal cancer, Phase I: Patients with relapsed or refractory locally advanced or metastatic solid tumors not amenable to standard systemic therapy., Phase II: Patients with relapsed or refractory locally advanced or metastatic colorectal cancer not amenable to standard systemic therapy.
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • L19TNFaDrug

    Phase I: Sequential assignment of Patient cohorts to one of six dose levels of L19TNFa: 1.3, 2.6, 5.2, 7.8, 10.4, 13.0 µg/kg.

    Phase II: The Recommended Dose (RD) of 13.0 µg/kg of L19TNFα determined in Phase I.

    Schedule: Infusions of L19TNFα on days 1, 3 and 5 of each 21-day cycle. Patients may remain on treatment for a maximum of six 21-day cycles.

Study groups in NCT01253837
Study groupRoleWhat they receive
L19TNFaExperimentalPhase I: Prospective, open-label, dose escalation study. Phase II: Prospective, single-arm, open-label study, equivalent to the stage 1 of the Simon two-stage phase II design.
Receives: Drug: L19TNFa

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I: Determination of the Maximum Tolerated Dose (MTD) and Recommended Dose (RD)

    Determination of the Maximum Tolerated Dose (MTD) and Recommended Dose (RD) of L19TNFα.

    Measured: day 1-29

  2. Phase II: Investigation of the anti-cancer activity of L19TNFα as measured by Objective Response Rate (ORR)

    Investigation of the anti-cancer activity of L19TNFα as monotherapy as measured by the Objective Response Rate (ORR) at the end of cycle 2 in subjects with relapsed or refractory locally advanced or metastatic colorectal cancer not amenable to standard systemic therapy.

    Measured: within day 42

Secondary outcomes (3)

  1. Investigation of serum concentrations of L19TNFα (pharmacokinetic properties)

    Measured: day 1-5

  2. Investigation of the induction of human anti-fusion protein antibody (HAFA)

    Measured: 1-16 months

  3. Investigation of early signs of anti-tumor activity of L19TNFα

    Investigation of early signs of anti-tumor activity of L19TNFα as measured by Objective Response Rate (ORR) at the end of cycle 2, median Progression-Free Survival (PFS) and median Overall Survival (OS).

    Measured: 14 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Dec 2010 (estimated)
  2. Study startSep 2007
  3. Primary completionMay 2011
  4. Study completionSep 2011

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01253837
Sponsor's protocol ID
PH-L19TNFα-02/07
Other IDs
2007-001157-26
Status last verified
Sep 2011
First submitted
2 Dec 2010
Last updated
23 Sep 2011
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing L19TNFa in people with Solid Tumors and Colorectal Cancer, 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 14 inclusion and 24 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 23 Sep 2011. 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 combined 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.

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?

Phase I: Determination of the Maximum Tolerated Dose (MTD) and Recommended Dose (RD) (time frame: day 1-29). 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 NCT01253837.

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 23 Sep 2011.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in