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Intratumoral Administration of Daromun in Non-melanoma Skin Cancer Patients (DUNCAN)

Primary Purpose

Carcinoma, Basal Cell, Carcinoma, Cutaneous Squamous Cell

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
L19IL2 +L19TNF
Sponsored by
Philogen S.p.A.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Basal Cell

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Sites / Locations

  • Universitätsklinikum AugsburgRecruiting
  • Charité Universitätsmedizin BerlinRecruiting
  • University Hospital Carl Gustav Carus
  • Universitätsklinikum Essen (AöR)Recruiting
  • Nationales Centrum für Tumorerkrankungen (NCT)Recruiting
  • University Medical Center Schleswig HolsteinRecruiting
  • Universitätsklinikum RegensburgRecruiting
  • Tübingen University HospitalRecruiting
  • Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie WarszawaRecruiting
  • Kantonsspital St.Gallen, Clinical Trials Unit, Dermatologie und VenerologieRecruiting
  • Universitätsspital Zürich (USZ)Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single arm

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Pathological Response
Efficacy of L19IL2/L19TNF measured as Pathological Response for each tumor type at the time of surgery.
Safety (AE)
Safety of intratumoral administration of L19IL2/L19TNF, assessed by Common Toxicity Criteria (version 5.0, CTCAE)
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
Safety: change in vital signs
Measurement of heart rate (beats per minute)
Safety: change in vital signs
Measurement of blood pressure (mmHg)

Full Information

First Posted
April 17, 2020
Last Updated
October 6, 2023
Sponsor
Philogen S.p.A.
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1. Study Identification

Unique Protocol Identification Number
NCT04362722
Brief Title
Intratumoral Administration of Daromun in Non-melanoma Skin Cancer Patients
Acronym
DUNCAN
Official Title
A Phase II Study of Intratumoral Administration of L19IL2/L19TNF in Non-melanoma Skin Cancer Patients With Presence of Injectable Lesions
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 2, 2020 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Philogen S.p.A.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Basal Cell, Carcinoma, Cutaneous Squamous Cell

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single arm
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
L19IL2 +L19TNF
Other Intervention Name(s)
bifikafusp alfa + onfekafusp alfa
Intervention Description
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.
Primary Outcome Measure Information:
Title
Efficacy of L19IL2/L19TNF in CR
Description
Objective Response Rate (Complete Response CR) for each tumor type from beginning of treatment according to RECIST v1.1 criteria.
Time Frame
Tumor Assessment/Safety visit (Week 6, Day 36)
Title
Efficacy of L19IL2/L19TNF in PR
Description
Objective Response Rate (Partial Response PR) for each tumor type from beginning of treatment according to RECIST v1.1 criteria.
Time Frame
Tumor Assessment/Safety visit (Week 6, Day 36)
Secondary Outcome Measure Information:
Title
Pathological Response
Description
Efficacy of L19IL2/L19TNF measured as Pathological Response for each tumor type at the time of surgery.
Time Frame
At Surgery
Title
Safety (AE)
Description
Safety of intratumoral administration of L19IL2/L19TNF, assessed by Common Toxicity Criteria (version 5.0, CTCAE)
Time Frame
Throughout study completion for each patient, an average of 12 weeks for each patient
Title
Safety: ECG
Description
Electrocardiogram (ECG) findings. In particular, data about QT/QTc intervals will be collected and analysed for QT/QTc prolongation potentially caused by treatment
Time Frame
Before first drug administration at Day 1 and at the Tumor Assessment Visit at Day 36 (Week 6).
Title
Safety: change in vital signs
Description
Measurement of heart rate (beats per minute)
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).
Title
Safety: change in vital signs
Description
Measurement of blood pressure (mmHg)
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).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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. Exclusion Criteria: 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Giuliano Elia, PhD
Phone
+3900577017816
Email
regulatory@philogen.com
First Name & Middle Initial & Last Name or Official Title & Degree
Marco Taras
Email
regulatory@philogen.com
Facility Information:
Facility Name
Universitätsklinikum Augsburg
City
Augsburg
ZIP/Postal Code
86179
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julia Welzel, Dr.
Facility Name
Charité Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Eigentler, Dr.
Facility Name
University Hospital Carl Gustav Carus
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Friedegund Meier, Dr.
Facility Name
Universitätsklinikum Essen (AöR)
City
Essen
ZIP/Postal Code
45147
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dirk Schadendorf, Dr.
Facility Name
Nationales Centrum für Tumorerkrankungen (NCT)
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jessica C. Hassel, Dr.
Facility Name
University Medical Center Schleswig Holstein
City
Kiel
ZIP/Postal Code
24105
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katharina C. Kahler, Dr.
Facility Name
Universitätsklinikum Regensburg
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sebastian Haferkamp, Dr.
Facility Name
Tübingen University Hospital
City
Tübingen
ZIP/Postal Code
D-72076
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lukas Flatz, MD
Facility Name
Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie Warszawa
City
Warsaw
ZIP/Postal Code
02-781
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Piotr Rutkowski, MD
Facility Name
Kantonsspital St.Gallen, Clinical Trials Unit, Dermatologie und Venerologie
City
Saint Gallen
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lukas Flatz, PhD, MD
Facility Name
Universitätsspital Zürich (USZ)
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Reinhard Dummer, Dr.

12. IPD Sharing Statement

Plan to Share IPD
No

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Intratumoral Administration of Daromun in Non-melanoma Skin Cancer Patients

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