Carcinoma, Basal CellPhase 2DUNCANNCT04362722
Intratumoral Administration of Daromun in Non-melanoma Skin Cancer Patients
A Phase 2 study testing L19IL2 +L19TNF in people with Carcinoma, Basal Cell and Carcinoma, Cutaneous Squamous Cell, run by Philogen S.p.A. at 11 sites in 3 countries.
Trial summary
This clinical phase II study is designed to investigate the efficacy of intratumorally administered L19IL2/L19TNF in patients with injectable lesions of BCC or cSCC. Favorable tumor responses following intralesional treatment with L19IL2/L19TNF have been observed in patients with injectable melanoma lesions of stage… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Carcinoma, Basal Cell, Carcinoma, Cutaneous Squamous Cell
- What is being tested?
- L19IL2 +L19TNF
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 11 sitesin 3 countries
- Study dates
- 2 Sep 2020to Sep 2024
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- High-risk, localized (non-metastatic, node negative, single or multifocal) BCC or cSCC amenable to intratumoral injection.
- Patients with injectable and measurable regional cutaneous or subcutaneous in-transit or satellite metastasis but without regional nodal involvement are also eligible.
- Male or female patients, age 18 - 100 years.
- ECOG Performance Status/WHO Performance Status ≤ 1.
- Hemoglobin > 10.0 g/dL.
- Platelets > 100 x 10^9/L.
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- ALT and AST, GGT and Lipase ≤ 1.5 x the upper limit of normal (ULN).
- Serum creatinine < 1.5 x ULN and GFR > 60 mL/min.
- All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v. 5.0) Grade ≤ 1 unless otherwise specified.
- Women of childbearing potential (WOCBP) must have negative pregnancy test results at screening. WOCBP must be using, from screening to three months following the last study drug administration, highly effective contraception methods, as defined by the "Recommendations for contraception and pregnancy testing in clinical trials" issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group and which include, for instance, progesterone-only or combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion, vasectomised partner.
- Male patients with WOCBP partners must agree to use simultaneously two acceptable methods of contraception (i.e. spermicidal gel plus condom) from the screening to three months following the last study drug administration.
- Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
Who cannot join
- Previous or concurrent cancer type that is distinct from the cancers being evaluated in this study, except any cancer curatively treated more than 2 years prior to study entry.
- Patients may have previously received topical or systemic chemotherapy, immunotherapy or radiation therapy on the tumor sites. Such therapies must be completed at least 4 weeks prior to study drug administration.
- Patients with node positive BCC/cSCC who are candidate to SHH inhibitor or checkpoint inhibitor therapy.
- Presence of active severe bacterial or viral infections or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study. In particular a documented test for HIV, HBV and HCV excluding active infection is needed.
- History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris, inadequately treated cardiac arrhythmias and heart insufficiency (any grade, New York Heart Association (NYHA) criteria).
- Any abnormalities observed during baseline ECG investigations that are considered clinically significant by the investigator.
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- Known arterial aneurysms.
- INR > 3.
- Uncontrolled hypertension.
- Known uncontrolled coagulopathy or bleeding disorder.
- Known hepatic cirrhosis or severe pre-existing hepatic impairment.
- Moderate to severe respiratory failure.
- Active autoimmune disease.
- Patient requires or is taking systemic corticosteroids (>5 mg/day) or other immunosuppressant drugs on a long-term basis. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions and asthma/COPD is not considered an exclusion criterion.
- Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies.
- Pregnancy or breast-feeding.
- Ischemic peripheral vascular disease (Grade IIb-IV).
- Severe diabetic retinopathy.
- Recovery from major trauma including surgery within 4 weeks prior to enrollment.
- Solid organ transplant recipient or patient with iatrogenic or pathologic severe immune suppression.
- Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.
Trial locations and contacts
11 sites in 3 countries.
Marco Taras contact
11 sites in 3 countries
Germany8 sites, 8 recruiting
- Recruiting
Universitätsklinikum Augsburg
Augsburg, 86179
Julia Welzel, Dr.
- Recruiting
Charité Universitätsmedizin Berlin
Berlin, 10117
Thomas Eigentler, Dr.
- Not yet recruiting
University Hospital Carl Gustav Carus
Dresden, 01307
Friedegund Meier, Dr.
- Recruiting
Universitätsklinikum Essen (AöR)
Essen, 45147
Dirk Schadendorf, Dr.
- Recruiting
Nationales Centrum für Tumorerkrankungen (NCT)
Heidelberg, 69120
Jessica C. Hassel, Dr.
- Recruiting
University Medical Center Schleswig Holstein
Kiel, 24105
Katharina C. Kahler, Dr.
- Recruiting
Universitätsklinikum Regensburg
Regensburg, 93053
Sebastian Haferkamp, Dr.
- Recruiting
Tübingen University Hospital
Tübingen, D-72076
Lukas Flatz, MD
Switzerland2 sites, 2 recruiting
- Recruiting
Kantonsspital St.Gallen, Clinical Trials Unit, Dermatologie und Venerologie
Sankt Gallen
Lukas Flatz, PhD, MD
- Recruiting
Universitätsspital Zürich (USZ)
Zurich, 8091
Reinhard Dummer, Dr.
Poland1 site, 1 recruiting
- Recruiting
Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie Warszawa
Warsaw, 02-781
Piotr Rutkowski, MD
About this study
Official title: A Phase II Study of Intratumoral Administration of L19IL2/L19TNF in Non-melanoma Skin Cancer Patients With Presence of Injectable Lesions
This clinical phase II study is designed to investigate the efficacy of intratumorally administered L19IL2/L19TNF in patients with injectable lesions of BCC or cSCC. Favorable tumor responses following intralesional treatment with L19IL2/L19TNF have been observed in patients with injectable melanoma lesions of stage III or IV, for injected and non-injected lesions.
The proposed clinical phase II study plans to investigate the intralesional administration of 6.5 Mio IU of L19IL2 (~1.08 mg) and 200 µg of L19TNF to be administered in an approximate volume of 1.0 mL as a single or multiple intratumoral injections in patients with high-risk BCC or cSCC.
There is a high medical need for non-invasive therapeutic strategies with a comparable good response rate and high recurrence free survival for treatment of patients with BCC or cSCC, who cannot be treated by or refuse surgery. Surgery is not always applicable, as it may not be feasible due to the anatomic location, may have a poor cosmetic outcome for the patient or is generally not accepted as treatment strategy by the patient. However, current non-surgical treatment strategies have a considerably reduced response rate and recurrence free survival. Based on the favorable results for injected and non-injected lesions obtained in the phase II study of L19IL2/L19TNF and the good safety profile seen in the subsequent phase III study, both in stage III or IV melanoma patients, we believe, that patients with BCC or cSCC will profit from intralesional treatment with L19IL2/L19TNF.
- Being tested
- L19IL2 +L19TNF
- Medical subject headings
- Carcinoma, Basal Cell, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L19IL2 +L19TNFDrug
Also called bifikafusp alfa + onfekafusp alfa
Single or multiple intratumoral administration of a mixture of L19IL2 and L19TNF will be performed once weekly for up to 4 weeks into all injectable lesions present at the beginning of treatment or appearing during treatment phase The dose will be constituted by 6.5 Mio IU L19IL2 (~1.08 mg) and 200 µg L19TNF.
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | 40 patients will be enrolled and treated with a mixture of 6.5 Mio IU (~1.08 mg) L19IL2 and 200 µg L19TNF once weekly for 4 consecutive weeks. The dose will be distributed among the lesions via multiple intralesional injections.
New lesions occurring during the treatment phase will also be treated as described but the treatment period for new lesions will not be extended beyond the previously defined 4 weeks treatment period with clock-start at the time of the first intralesional L19IL2/L19TNF injection.
After the Tumor Assessment/Safety visit, patients may receive surgery in a curative intention within 6 weeks, in order to assess the pathological response with estimation of percent of residual viable tumor cells. Receives: Drug: L19IL2 +L19TNF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of L19IL2/L19TNF in CR
Objective Response Rate (Complete Response CR) for each tumor type from beginning of treatment according to RECIST v1.1 criteria.
Measured: Tumor Assessment/Safety visit (Week 6, Day 36)
Efficacy of L19IL2/L19TNF in PR
Objective Response Rate (Partial Response PR) for each tumor type from beginning of treatment according to RECIST v1.1 criteria.
Measured: Tumor Assessment/Safety visit (Week 6, Day 36)
Secondary outcomes (5)
Pathological Response
Efficacy of L19IL2/L19TNF measured as Pathological Response for each tumor type at the time of surgery.
Measured: At Surgery
Safety (AE)
Safety of intratumoral administration of L19IL2/L19TNF, assessed by Common Toxicity Criteria (version 5.0, CTCAE)
Measured: Throughout study completion for each patient, an average of 12 weeks for each patient
Safety: ECG
Electrocardiogram (ECG) findings. In particular, data about QT/QTc intervals will be collected and analysed for QT/QTc prolongation potentially caused by treatment
Measured: Before first drug administration at Day 1 and at the Tumor Assessment Visit at Day 36 (Week 6).
Safety: change in vital signs
Measurement of heart rate (beats per minute)
Measured: Before first drug administration at Day 1, Day 8, Day 15, Day 22 and at the Tumor Assessment Visit at Day 36 (Week 6).
Safety: change in vital signs
Measurement of blood pressure (mmHg)
Measured: Before first drug administration at Day 1, Day 8, Day 15, Day 22 and at the Tumor Assessment Visit at Day 36 (Week 6).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2020
- Study start2 Sep 2020
- Primary completionSep 2024 (estimated)
- Study completionSep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Basal CellStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
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
- NCT04362722
- Sponsor's protocol ID
- PH-L19IL2TNFNMSC-04/19
- Acronym
- DUNCAN
- Status last verified
- Oct 2023
- First submitted
- 17 Apr 2020
- Last updated
- 10 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Intratumoral Administration of L19IL2/L19TNF in Non-melanoma Skin Cancer Patients With Presence of Injectable Lesions
- ClinicalTrials.gov ID
- NCT04362722
- Acronym / sponsor ID
- DUNCAN / PH-L19IL2TNFNMSC-04/19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Philogen S.p.A.Industry (pharma, biotech, devices)
- Study start
- 2 Sep 2020 (actual)
- Primary completion
- Sep 2024 (estimated)
- Study completion
- Sep 2024 (estimated)
- First posted
- 27 Apr 2020 (actual)
- 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.
This clinical phase II study is designed to investigate the efficacy of intratumorally administered L19IL2/L19TNF in patients with injectable lesions of BCC or cSCC. Favorable tumor responses following intralesional treatment with L19IL2/L19TNF have been observed in patients with injectable melanoma lesions of stage III or IV, for injected and non-injected lesions.
The proposed clinical phase II study plans to investigate the intralesional administration of 6.5 Mio IU of L19IL2 (~1.08 mg) and 200 µg of L19TNF to be administered in an approximate volume of 1.0 mL as a single or multiple intratumoral injections in patients with high-risk BCC or cSCC.
There is a high medical need for non-invasive therapeutic strategies with a comparable good response rate and high recurrence free survival for treatment of patients with BCC or cSCC, who cannot be treated by or refuse surgery. Surgery is not always applicable, as it may not be feasible due to the anatomic location, may have a poor cosmetic outcome for the patient or is generally not accepted as treatment strategy by the patient. However, current non-surgical treatment strategies have a considerably reduced response rate and recurrence free survival. Based on the favorable results for injected and non-injected lesions obtained in the phase II study of L19IL2/L19TNF and the good safety profile seen in the subsequent phase III study, both in stage III or IV melanoma patients, we believe, that patients with BCC or cSCC will profit from intralesional treatment with L19IL2/L19TNF.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Drug: L19IL2 +L19TNF40 patients will be enrolled and treated with a mixture of 6.5 Mio IU (~1.08 mg) L19IL2 and 200 µg L19TNF once weekly for 4 consecutive weeks. The dose will be distributed among the lesions via multiple intralesional injections. New lesions occurring during the treatment phase will also be treated as described but the treatment period for new lesions will not be extended beyond the previously defined 4 weeks treatment period with clock-start at the time of the first intralesional L19IL2/L19TNF injection. After the Tumor Assessment/Safety visit, patients may receive surgery in a curative intention within 6 weeks, in order to assess the pathological response with estimation of percent of residual viable tumor cells. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- High-risk, localized (non-metastatic, node negative, single or multifocal) BCC or cSCC amenable to intratumoral injection.
- Patients with injectable and measurable regional cutaneous or subcutaneous in-transit or satellite metastasis but without regional nodal involvement are also eligible.
- Male or female patients, age 18 - 100 years.
- ECOG Performance Status/WHO Performance Status ≤ 1.
- Hemoglobin > 10.0 g/dL.
Key exclusion criteria (21 listed)
- Previous or concurrent cancer type that is distinct from the cancers being evaluated in this study, except any cancer curatively treated more than 2 years prior to study entry.
- Patients may have previously received topical or systemic chemotherapy, immunotherapy or radiation therapy on the tumor sites. Such therapies must be completed at least 4 weeks prior to study drug administration.
- Patients with node positive BCC/cSCC who are candidate to SHH inhibitor or checkpoint inhibitor therapy.
- Presence of active severe bacterial or viral infections or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study. In particular a documented test for HIV, HBV and HCV excluding active infection is needed.
- History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris, inadequately treated cardiac arrhythmias and heart insufficiency (any grade, New York Heart Association (NYHA) criteria).
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 +L19TNFAlso: bifikafusp alfa + onfekafusp alfaSingle or multiple intratumoral administration of a mixture of L19IL2 and L19TNF will be performed once weekly for up to 4 weeks into all injectable lesions present at the beginning of treatment or appearing during treatment phase The dose will be constituted by 6.5 Mio IU L19IL2 (~1.08 mg) and 200 µg L19TNF. | Drug | Single arm |
Primary outcome
Efficacy of L19IL2/L19TNF in CR
Time frame: Tumor Assessment/Safety visit (Week 6, Day 36)
Objective Response Rate (Complete Response CR) for each tumor type from beginning of treatment according to RECIST v1.1 criteria.
Efficacy of L19IL2/L19TNF in PR
Time frame: Tumor Assessment/Safety visit (Week 6, Day 36)
Objective Response Rate (Partial Response PR) for each tumor type from beginning of treatment according to RECIST v1.1 criteria.
5 secondary outcomes
Pathological Response
Time frame: At Surgery
Safety (AE)
Time frame: Throughout study completion for each patient, an average of 12 weeks for each patient
Safety: ECG
Time frame: Before first drug administration at Day 1 and at the Tumor Assessment Visit at Day 36 (Week 6).
Safety: change in vital signs
Time frame: Before first drug administration at Day 1, Day 8, Day 15, Day 22 and at the Tumor Assessment Visit at Day 36 (Week 6).
Safety: change in vital signs
Time frame: Before first drug administration at Day 1, Day 8, Day 15, Day 22 and at the Tumor Assessment Visit at Day 36 (Week 6).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2023.
- Individual participant dataSharing planned: No
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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.
Marco Taras contact
11 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing L19IL2 +L19TNF in people with Carcinoma, Basal Cell and Carcinoma, Cutaneous Squamous Cell, run by Philogen S.p.A. at 11 sites in 3 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 12 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: status not confirmed, as of the sponsor's last update on 10 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Germany, Switzerland, Poland. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Giuliano Elia, PhD (+3900577017816, regulatory@philogen.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of L19IL2/L19TNF in CR (time frame: Tumor Assessment/Safety visit (Week 6, Day 36)). 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?
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 10 Oct 2023.