Pancreatic Cancer Patients Diagnosed With Locally Advanced or Metastatic Pancreatic Cancer Not Amenable to Curative Surgical ResectionPhase 1NCT01198522
Combination Therapy of L19IL2 and Gemcitabine in Advanced Pancreatic Cancer Patients
A Phase 1 study testing L19IL2 monoclonal antibody-cytokine fusion protein in combination with gemcitabine in people with Pancreatic Cancer Patients Diagnosed With Locally Advanced or Metastatic Pancreatic Cancer Not Amenable to Curative Surgical Resection, run by Philogen S.p.A. at 5 sites in 2 countries.
Trial summary
Systemic treatment for advanced, non-resectable pancreatic cancer still having minimal impact on the survival of patients. Even with the application of more potent gemcitabine-based regimens, survival of more than 1 year is uncommon for advanced disease. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Pancreatic Cancer Patients Diagnosed With Locally Advanced or Metastatic Pancreatic Cancer Not Amenable to Curative Surgical Resection
- What is being tested?
- L19IL2 monoclonal antibody-cytokine fusion protein in combination with gemcitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 5 sitesin 2 countries
- Study dates
- Jun 2007to Nov 2014
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed solid cancer of any pathology or adenocarcinoma of the pancreas with evidence of locally advanced (non resectable Stage II or III) or metastatic disease (Stage IV).
- For advanced solid cancer patients (part A), who may have received previous chemotherapy or radiation therapy, but must be amenable for a gemcitabine treatment according to the discretion of the principal investigator.
- For pancreatic cancer patients who may have received previous chemotherapy against pancreatic cancer or local radiation for palliation if the irradiated area was not the only source of measurable or assessable disease.
- ECOG performance status ≤1.
- Patients aged >/= 18 and </= 70 years.
- Patients must have at least one uni-dimensionally measurable lesion by computed tomography as defined by RECIST V1.1 criteria. This lesion must not have been irradiated during previous treatments.
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- All acute toxic effects (excluding alopecia) of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v3.0) Grade ≤ 1.
- Sufficient hematologic, liver and renal function:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, platelets ≥ 100 x 10^9/L, haemoglobin (Hb) ≥ 9.5 g/dl.
- Alkaline phosphatase (AP), alanine aminotransferase (ALT) and or aspartate aminotransferase ≤ 3 x upper limit of reference range (ULN), and total bilirubin ≤ 2.0 mg/gL unless liver involvement by the tumor, in which case the transaminase levels could be up to 5 x ULN.
- Creatinine ≤ 1.5 ULN or 24 h creatinine clearance ≥ 50 mL/min.
- Life expectancy of at least 12 weeks.
- Documented negative test for human immunodeficiency virus.
- Negative serum pregnancy test for females of childbearing potential within 14 days of starting treatment.
- If of childbearing potential, agreement must be made to use adequate contraceptive methods (e.g., oral contraceptives, condoms, or other adequate barrier controls, intrauterine contraceptive devices, or sterilization) beginning at the screening visit and continuing until 3 months following last treatment with study drug.
- Evidence of a personally signed and dated Ethics Committee-approved Informed Consent 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.
Who cannot join
- Presence of active infections (e.g. requiring antibiotic 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.
- 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 or PR after radiotherapy) is allowed.
- Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study, or any cancer curatively treated ≥ 2 yeast prior to study entry, except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumours (TA, TIs \&TI).
- History of chronic hepatitis B or C, or chronic active hepatitis or active autoimmune diseases.
- History of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
- Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).
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- Irreversible cardiac arrhythmias requiring permanent medication.
- Uncontrolled hypertension.
- Ischemic peripheral vascular disease (Grade IIb-IV).
- Severe rheumatoid arthritis.
- Severe diabetic retinopathy.
- History of allograft or stem cell transplantation
- Major trauma including surgery within 4 weeks of administration of study treatment.
- Known history of allergy to IL2, gemcitabine, or other intravenously administered human proteins/peptides/antibodies.
- Pregnancy or breast feeding. Female patient must agree to use effective contraception, or be surgically sterile or postmenopausal. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
- Chemotherapy (standard or experimental) or radiation therapy within 4 weeks of the administration 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 of the administration of study treatment.
- 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. A maximum dose per day of 5 mg prednisone (or equivalent), when it is meant to address cancer symptoms (e.g., pain, dyspnoea, lack of appetite), is allowed. A suspected presence of chronic inflammatory disease has to be considered an exclusion criterion.
- Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.
- Persons who are interned in Institutions by Judiciary or other Authorities
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
Italy3 sites
Mater Salutis Hospital
Legnago
European Institute of Oncology
Milan
Azienda Ospedaliera Universitaria Senese
Siena
Germany2 sites
Campus Charité Virchow Klinikum
Berlin
National Center for Tumor Diseases (NCT)
Heidelberg
About this study
Official title: Phase I Study of the Tumor-targeting Human L19IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Gemcitabine in Patients With Advanced Pancreatic Cancer
Systemic treatment for advanced, non-resectable pancreatic cancer still having minimal impact on the survival of patients. Even with the application of more potent gemcitabine-based regimens, survival of more than 1 year is uncommon for advanced disease. Accordingly, there is substantial unmet needs for the improvement of treatment options. The combination and simultaneous application of tumor-targeted L19IL2 with gemcitabine could result in improved anti-cancer efficacy, based on preliminary clinical and strong preclinical data.
The primary purpose of this Phase I study is to define a safe and potentially more active treatment regimen of L19IL2 (escalating doses) combined with gemcitabine for advanced pancreatic cancer patients. Also, early signs of anticancer responses of the L19IL2/gemcitabine regimen will be assessed and compared to historical controls (gemcitabine monotherapy).
- Being tested
- L19IL2 monoclonal antibody-cytokine fusion protein in combination with gemcitabine
- Keywords
- Interleukin, IL2, Gemcitabine, monoclonal, antibody, cytokine, tumour targeting, dose finding, fusion protein, Pancreatic cancer,, L19
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L19IL2 monoclonal antibody-cytokine fusion protein in combination with gemcitabineDrug
Part A) Patient cohorts will sequentially be assigned to 800 or 1,000 mg/m2 of gemcitabine. gemcitabine will be given in combination with a fixed dose of L19IL2. Part B) Patient cohorts will sequentially be assigned to 10, 15,22.5,30 or 37,5 MioIU IL2 equivalents of L19IL2. L19IL2 will be given in combination with gemcitabine at the dose recommended from Part A. Should the MTD of L19IL2 not be reached within the planned cohorts listed above, the dose of L19IL2 will be further increased following 7.5 MioIU increasing steps.
Induction treatment: Intravenous (i.v.) infusions of L19IL2 on days 1,3,5,22,24, 26,43,45,47, followed by i.v. infusions of gemcitabine on days 1,8,15,22,29,36,43. Maintenance treatment: Patients with objective tumor responses or stable disease will receive up to 4 cycles of maintenance treatment, starting on day 57: i.v. infusions of L19IL2 on days 1 (day 57), 8,15, followed by an i.v. infusion of gemcitabine. Treatment cycles will be repeated on day 29.
| Study group | Role | What they receive |
|---|---|---|
| Therapy of L19IL2 and Gemcitabine | Other | Dose escalation study. Part A) Gemcitabine dose escalation. Part B) L19IL2 dose escalation. Receives: Drug: L19IL2 monoclonal antibody-cytokine fusion protein in combination with gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose and the preliminary tolerability profile.
Establishment of the maximum tolerated dose (MTD) and the preliminary tolerability profile of L19IL2 and gemcitabine including the recommended phase II doses (RD) when used in combination.
Measured: 49 days
Secondary outcomes (3)
Pharmacokinetics
Investigation of the pharmacokinetics of L19IL2 and gemcitabine when given as a combination.
Measured: 4 weeks
Human anti-fusion protein antibodies
Investigation of the induction of human anti-fusion protein antibodies (HAFA) levels.
Measured: 18 months
Antitumor activity
Investigation of the antitumor activity of the combination of L19IL2 and gemcitabine in previously treated and untreated locally advanced or metastatic pancreatic cancer patients.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2010 (estimated)
- Study startJun 2007
- Primary completionNov 2014
- Study completionNov 2014
Why it stopped: lack of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic Cancer Patients Diagnosed With Locally Advanced or Metastatic Pancreatic Cancer Not Amenable to Curative Surgical ResectionStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Philogen S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01198522
- Sponsor's protocol ID
- PH-L19IL2GEM-01/07
- Other IDs
- 2007-001609-81
- Status last verified
- Oct 2014
- First submitted
- 8 Sep 2010
- Last updated
- 15 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
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 I Study of the Tumor-targeting Human L19IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Gemcitabine in Patients With Advanced Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT01198522
- Acronym / sponsor ID
- PH-L19IL2GEM-01/07
- Keywords
- Interleukin, IL2, Gemcitabine, monoclonal, antibody, cytokine, tumour targeting, dose finding, fusion protein, Pancreatic cancer,, L19
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of recruitment
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Philogen S.p.A.Industry (pharma, biotech, devices)
- Study start
- Jun 2007
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 10 Sep 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.
Systemic treatment for advanced, non-resectable pancreatic cancer still having minimal impact on the survival of patients. Even with the application of more potent gemcitabine-based regimens, survival of more than 1 year is uncommon for advanced disease. Accordingly, there is substantial unmet needs for the improvement of treatment options. The combination and simultaneous application of tumor-targeted L19IL2 with gemcitabine could result in improved anti-cancer efficacy, based on preliminary clinical and strong preclinical data.
The primary purpose of this Phase I study is to define a safe and potentially more active treatment regimen of L19IL2 (escalating doses) combined with gemcitabine for advanced pancreatic cancer patients. Also, early signs of anticancer responses of the L19IL2/gemcitabine regimen will be assessed and compared to historical controls (gemcitabine monotherapy).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Therapy of L19IL2 and Gemcitabine | Other | Drug: L19IL2 monoclonal antibody-cytokine fusion protein in combination with gemcitabineDose escalation study. Part A) Gemcitabine dose escalation. Part B) L19IL2 dose escalation. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Histologically or cytologically confirmed solid cancer of any pathology or adenocarcinoma of the pancreas with evidence of locally advanced (non resectable Stage II or III) or metastatic disease (Stage IV).
- For advanced solid cancer patients (part A), who may have received previous chemotherapy or radiation therapy, but must be amenable for a gemcitabine treatment according to the discretion of the principal investigator.
- For pancreatic cancer patients who may have received previous chemotherapy against pancreatic cancer or local radiation for palliation if the irradiated area was not the only source of measurable or assessable disease.
- ECOG performance status ≤1.
- Patients aged >/= 18 and </= 70 years.
Key exclusion criteria (21 listed)
- Presence of active infections (e.g. requiring antibiotic 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.
- 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 or PR after radiotherapy) is allowed.
- Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study, or any cancer curatively treated ≥ 2 yeast prior to study entry, except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumours (TA, TIs \&TI).
- History of chronic hepatitis B or C, or chronic active hepatitis or active autoimmune diseases.
- History of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
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 |
|---|---|---|
| L19IL2 monoclonal antibody-cytokine fusion protein in combination with gemcitabinePart A) Patient cohorts will sequentially be assigned to 800 or 1,000 mg/m2 of gemcitabine. gemcitabine will be given in combination with a fixed dose of L19IL2. Part B) Patient cohorts will sequentially be assigned to 10, 15,22.5,30 or 37,5 MioIU IL2 equivalents of L19IL2. L19IL2 will be given in combination with gemcitabine at the dose recommended from Part A. Should the MTD of L19IL2 not be reached within the planned cohorts listed above, the dose of L19IL2 will be further increased following 7.5 MioIU increasing steps. Induction treatment: Intravenous (i.v.) infusions of L19IL2 on days 1,3,5,22,24, 26,43,45,47, followed by i.v. infusions of gemcitabine on days 1,8,15,22,29,36,43. Maintenance treatment: Patients with objective tumor responses or stable disease will receive up to 4 cycles of maintenance treatment, starting on day 57: i.v. infusions of L19IL2 on days 1 (day 57), 8,15, followed by an i.v. infusion of gemcitabine. Treatment cycles will be repeated on day 29. | Drug | Therapy of L19IL2 and Gemcitabine |
Primary outcome
Maximum tolerated dose and the preliminary tolerability profile.
Time frame: 49 days
Establishment of the maximum tolerated dose (MTD) and the preliminary tolerability profile of L19IL2 and gemcitabine including the recommended phase II doses (RD) when used in combination.
3 secondary outcomes
Pharmacokinetics
Time frame: 4 weeks
Human anti-fusion protein antibodies
Time frame: 18 months
Antitumor activity
Time frame: 18 months
Results and safety
The study was stopped early (reason given: lack of recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2022.
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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.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing L19IL2 monoclonal antibody-cytokine fusion protein in combination with gemcitabine in people with Pancreatic Cancer Patients Diagnosed With Locally Advanced or Metastatic Pancreatic Cancer Not Amenable to Curative Surgical Resection, run by Philogen S.p.A. at 5 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 21 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: stopped early, 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 5 sites in Italy, Germany. 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 was stopped early (reason given: lack of recruitment). Results are not available in the source record.
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?
Maximum tolerated dose and the preliminary tolerability profile. (time frame: 49 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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; AzTrials last refreshed its copy on 8 Nov 2026.