AzTrials
AzTrials

Advanced Solid Tumors Amenable to Anthracycline TherapyPhase 1NCT02076620

L19TNFα in Combination With Doxorubicin in Patients With Advanced Solid Tumours

A Phase 1 study testing L19TNFα and Doxorubicin in people with Advanced Solid Tumors Amenable to Anthracycline Therapy and Sarcoma, Breast Cancer, Lung Carcinomas, and Gynecological Cancer Amenable to Anthracycline Therapy, run by Philogen S.p.A. at 2 sites in 2 countries.

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

Prospective, open-label, non randomized, dose escalation study that will be conducted in sequential cohorts of patients. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
L19TNFα and Doxorubicin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
2 sitesin 2 countries
Study dates
16 Jan 2013to 25 Jan 2018
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

  • Patients with histologically or cytologically confirmed advanced solid cancer deemed suitable for combination therapy of L19TNFα and doxorubicin.
  • Patients aged ≥18 years old with advanced or metastatic solid tumor in whom standard anticancer therapies have been exhausted and who are amenable for a doxorubicin monotherapy according to the discretion of the Principal Investigators and previously treated with a cumulative dose of anthracyclines (≤ 300 mg/m2).
  • Eastern cooperative oncology group (ECOG) performance status ≤ 2.
  • Patients may have received previous chemotherapy (>4 weeks prior therapy) or radiation therapy (>6 weeks prior therapy), but they must be amenable for doxorubicin treatment according to the discretion of the Principal Investigator.
  • Patients must have at least one unidimensionally measurable lesion by computed tomography as defined by RECIST criteria version 1.1. This lesion must not have been irradiated during previous treatments.
  • Previous anthracycline therapy, including liposomal doxorubicin, for metastatic and/or adjuvant disease is allowed. However, patients must not have received a cumulative anthracycline dose of more than 300 mg/m2 of doxorubicin, nor more than 500 mg/m2 of epirubicin, nor more than 600 mg/m2 of pegylated or non-pegylated liposomal doxorubicin prior to study entry, in order to avoid anthracycline-associated cardiotoxicity.
Show all 17Show fewer
  • Life expectancy more than 3 months.
  • 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 resolved to ≤ Grade 1, except elevated liver transaminases judged to be associated with tumor infiltration (see below) (graded according to the National Cancer Institute CTCAE v.4.02 dated September 15, 2009).
  • 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 patient to practice medically appropriate/acceptable method of birth control beginning 30 days before study entry and continuing until 6 months following the last treatment with study drug. Excluding women without childbearing potential; menopause at least 2 years earlier, tubal ligation at least 1 year earlier, or total hysterectomy. The definition of effective contraception will be based on the guidelines ICH M3 rev2.
  • Evidence of a personally signed and dated EC-approved ICF indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the study.
  • Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
  • ICF must be obtained for all the patients before enrollment into the study.

Who cannot join

  • Pregnancy or breast-feeding. Patients must agree to use effective contraception, or be surgically sterile or postmenopausal. The definition of effective contraception will be based on the guidelines ICH M3 rev2.
  • 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.
  • Presence of known brain metastases. If patient is symptomatic, negative CT scan within two months before study beginning is required. However, presence of controlled brain metastases (i.e., evaluated as SD of PR after radiotherapy) is allowed.
  • Known cancer of other primary origin within the prior 5 years.
  • History of chronic hepatitis B or C, or chronic active hepatitis or active autoimmune diseases.
  • Cardiac disease as manifested by any of the following:
Show all 28Show fewer
  • > Grade II heart failure, graded per New York Heart Association (NYHA) criteria.
  • History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
  • Irreversible cardiac arrhythmias requiring permanent medication.
  • Ejection fraction less than the institutional lower limit of normal as assessed by MUGA scan or echocardiogram.
  • Uncontrolled hypertension.
  • Ischemic peripheral vascular disease (Grade IIb-IV).
  • Severe rheumatoid arthritis.
  • Severe diabetic retinopathy.
  • History of allograft or stem cell transplantation.
  • Major surgery or trauma within 4 weeks prior to start of study treatment.
  • Known history of allergy to TNFα, Anthracyclines or other intravenously administered human proteins/peptides/antibodies.
  • Chemotherapy (standard or experimental), or therapy with an investigational agent within 4 weeks prior to start of study treatment, and radiation within 6 weeks prior therapy.
  • Cumulative exposure to anthracycline-containing chemotherapy (patients received a cumulative anthracycline dose of more than 300 mg/m2 of doxorubicin or of more than 500 mg/m2 of epirubicin or pegylated or non-pegylated liposomal doxorubicin), prior to study entry precluding the application of at least an additional 150 mg/m2 doxorubicin (total dose for 2 cycles of study therapy).
  • Treatment with an investigational study drug within six weeks before beginning of treatment with L19TNFα.
  • 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.
  • Neuropathy > Grade 1.
  • Patient 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 anticoagulants at full dose .
  • Participation in another interventional clinical trial during participation in this trial.
  • Expectation that the patient 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 2 countries.

2 sites in 2 countries

Germany1 site

  • Universitätsklinikum Münster

    Münster

Other trials in Germany

Italy1 site

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan

Other trials in Italy

About this study

Official title: Phase I Study of the Tumor-targeting Human L19TNFα Monoclonal Antibody-cytokine Fusion Protein in Combination With Doxorubicin in Patients With Advanced Solid Tumours

Prospective, open-label, non randomized, dose escalation study that will be conducted in sequential cohorts of patients.

Read the detailed description

In the clinical trial 3-6 patients will be assigned to L19TNFalfa at one of the following sequential dose levels (10.4 µg/kg, 13 µg/kg and 17 µg/kg) in combination with a fixed dose of doxorubicin.

The RD will be defined following a traditional 3+3 design. The dose escalation will continue until the MTD is found, that is until at least two patients among a cohort of three to six patients experience a dose limiting toxicity (DLT).

Being tested
L19TNFα, Doxorubicin
Keywords
L19, monoclonal, antibody, doxorubicin, TNFα, solid tumour, sarcoma, breast cancer, lung carcinomas, gynecological cancer, anthracycline
Medical subject headings
Sarcoma, Breast Neoplasms

What participants receive

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

  • L19TNFαDrug

    L19TNFα will be administered as a 2 hours i.v. infusion on days 1, 3, and 5 of each 3-week cycle.

  • DoxorubicinDrug

    Doxorubicin will be administered as a 15 minutes i.v. infusion on day 1 of each 3-week cycle prior L19TNFα administration.

Study groups in NCT02076620
Study groupRoleWhat they receive
L19TNFα + doxorubicinExperimentalOnly one arm is specified. Patients will be treated in three cohorts with 3 different dosages of L19TNFα in combination with 60 mg/m2 of doxorubicin, according to the following study design: cohort 1 --> 10.4 μg/kg L19TNFα + doxorubicin; cohort 2 --> 13 μg/kg L19TNFα + doxorubicin; cohort 3 --> 17 μg/kg L19TNFα + doxorubicin.
Receives: Drug: L19TNFα; Drug: Doxorubicin

What is being measured

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

  1. Dose limiting toxicity (DLT)

    To assess the safety, including maximum tolerated dose (MTD), recommended dose (RD) and dose limiting toxicity (DLT) of L19TNFα in combination with doxorubicin, the following will be considered:

    • Adverse Events (AEs) assessment based on CTCAE v.4.03, including DLT assessment.
    • Standard laboratory (haematology, biochemistry and urinalysis) parameters.
    • Physical examination findings including assessment of vital signs and physical measurements (blood pressure, heart rate, body weight).

    Measured: From day 1 to day 29

Secondary outcomes (5)

  1. Pharmacokinetics assessment of L19TNFα

    Measured: At day 1 of week 1

  2. Human anti-fusion protein antibodies (HAFA) levels

    Investigate the potential induction of human anti-fusion protein antibodies (HAFA) through standard laboratory analysis.

    Measured: 1) at day 1, 2) at day 22, 3) at day 43, 4) at day 64, 5) at day 85, 6) at day 106, 7) from day 31 up to day 143, 8) from day 73 up to day 185

  3. Objective response rate (ORR)

    To investigate the antitumor activity

    Measured: Up to 1 year

  4. Median progression free survival (mPFS)

    To investigate the antitumor activity

    Measured: Up to 1 year

  5. Median overall survival (OS)

    To investigate the antitumor activity

    Measured: Up to 1 year

Timeline

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

  1. First posted3 Mar 2014 (estimated)
  2. Study start16 Jan 2013
  3. Primary completion25 Jan 2018
  4. Study completion25 Jan 2018

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02076620
Sponsor's protocol ID
PH-L19TNFDOXO-01/12
Other IDs
2012-000950-75
Status last verified
Apr 2022
First submitted
24 Feb 2014
Last updated
4 Apr 2022
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing L19TNFα and Doxorubicin in people with Advanced Solid Tumors Amenable to Anthracycline Therapy and Sarcoma, Breast Cancer, Lung Carcinomas, and Gynecological Cancer Amenable to Anthracycline Therapy, run by Philogen S.p.A. at 2 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 28 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 4 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 Germany, 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?

Dose limiting toxicity (DLT) (time frame: From day 1 to day 29). 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 NCT02076620.

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 4 Apr 2022.

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

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in