RECRUITING

Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C/D Melanoma Patients

Conditions

Melanoma Stage IIIB Melanoma Stage IIIC Melanoma Stage IIID

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The trial aims to evaluate the efficacy of Daromun neoadjuvant treatment followed by surgery and adjuvant therapy to improve in a statistically significant manner the recurrence-free survival (RFS) of Stage IIIB/C/D melanoma patients with respect to the standard of care (surgery and adjuvant therapy).

Official Title

An Open-Label, Randomized, Controlled Multi-Center Study of The Efficacy of Daromun (L19IL2 + L19TNF) Neoadjuvant Intratumoral Treatment Followed by Surgery and Adjuvant Therapy Versus Surgery and Adjuvant Therapy in Clinical Stage IIIB/C/D Melanoma Patients

Quick Facts

Study Start:2018-09-20

Study Completion:2031-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03567889

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Histologically or cytologically confirmed diagnosis of clinical stage IIIB, IIIC, and IIID (AJCC 8th edition) locoregional melanoma that is eligible for complete surgical resection of all metastases (surgically resectable). 2. Eligible subjects must have measurable disease and must be candidate for intralesional therapy with at least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (≥ 10 mm in longest diameter) or with multiple injectable lesions that in aggregate have a longest diameter of ≥ 10 mm. 3. Prior anti-tumor treatment for the primary melanoma lesion, including surgery and approved adjuvant treatments (e.g., radiotherapy, immune checkpoint inhibitors, BRAF/MEK inhibitors, etc.) is allowed. Before enrollment in the study, a wash-out period of 6 weeks is required and toxicities from prior treatments should be resumed to Grade ≤1. 4. Males or females, age ≥ 18 years. 5. ECOG Performance Status/WHO Performance Status ≤ 1. 6. Life expectancy of \> 24 months. 7. Absolute neutrophil count \> 1.5 x 109/L. 8. Hemoglobin \> 9.0 g/dL. 9. Platelets \> 100 x 109/L. 10. Total bilirubin ≤ 30 μmol/L (or ≤ 2.0 mg/dl). 11. ALT and AST ≤ 2.5 x the upper limit of normal (ULN). 12. Serum creatinine \< 1.5 x ULN. 13. LDH serum level ≤ 1.5 x ULN. 14. Documented negative test for HIV, HBV and HCV. For HBV serology, the determination of HBsAg and anti-HBcAg Ab is required. In patients with serology documenting previous exposure to HBV (i.e. positive anti-HBsAg with not vaccination and/or positive anti-HBcAg Ab), negative serum HBV-DNA is also required. 15. 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) (v4.03) Grade ≤ 1 unless otherwise specified above. 16. All women of childbearing potential (WOCBP) must have negative pregnancy test results at the screening. WOCBP must be using, from the screening to three months following the last study drug administration, highly effective contraception methods. WOCBP and effective contraception methods are 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, vasectomized partner or sexual abstinence. Pregnancy test will be repeated at the safety visit (only WOCBP and only for patients in Arm 1). 17. 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. 18. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. 19. Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures. 1. Uveal melanoma or mucosal melanoma 2. Evidence of distant metastases at screening. 3. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except: cervical carcinoma in situ, curatively treated basal cell carcinoma, superficial bladder tumors (Ta, Tis \& T1), second primary melanoma in situ or any cancer curatively treated ≥ 5 years prior to study entry. 4. Presence of active infections (e.g. requiring antimicrobial 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. 5. History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris. 6. Inadequately controlled cardiac arrhythmias including atrial fibrillation. 7. Heart insufficiency (\> Grade II, New York Heart Association (NYHA) criteria). 8. LVEF ≤ 50% and/or abnormalities observed during baseline ECG and Echocardiogram investigations that are considered as clinically significant by the investigator. 9. Uncontrolled hypertension. 10. Ischemic peripheral vascular disease (Grade IIb-IV). 11. Severe diabetic retinopathy. 12. Active autoimmune disease. 13. History of organ allograft or stem cell transplantation. 14. Recovery from major trauma including surgery within 4 weeks prior to enrollment. 15. Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies or any other constituent of the product. 16. Breast feeding female. 17. Anti-tumor therapy (except small surgery) within 4 weeks before enrollment. 18. Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before enrollment. 19. Planned administration of growth factors or immunomodulatory agents within 7 days before enrollment. 20. Patient requiring or taking corticosteroids or other immunosuppressant drugs on a long-term basis will be evaluated case by case with the Sponsor for inclusion/exclusion in the study. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criteria. 21. Any conditions that in the opinion of the investigator could hamper compliance with the study protocol. 22. Previous enrolment and randomization in the same study.	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion Criteria

1. Histologically or cytologically confirmed diagnosis of clinical stage IIIB, IIIC, and IIID (AJCC 8th edition) locoregional melanoma that is eligible for complete surgical resection of all metastases (surgically resectable).
2. Eligible subjects must have measurable disease and must be candidate for intralesional therapy with at least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (≥ 10 mm in longest diameter) or with multiple injectable lesions that in aggregate have a longest diameter of ≥ 10 mm.
3. Prior anti-tumor treatment for the primary melanoma lesion, including surgery and approved adjuvant treatments (e.g., radiotherapy, immune checkpoint inhibitors, BRAF/MEK inhibitors, etc.) is allowed. Before enrollment in the study, a wash-out period of 6 weeks is required and toxicities from prior treatments should be resumed to Grade ≤1.
4. Males or females, age ≥ 18 years.
5. ECOG Performance Status/WHO Performance Status ≤ 1.
6. Life expectancy of \> 24 months.
7. Absolute neutrophil count \> 1.5 x 109/L.
8. Hemoglobin \> 9.0 g/dL.
9. Platelets \> 100 x 109/L.
10. Total bilirubin ≤ 30 μmol/L (or ≤ 2.0 mg/dl).
11. ALT and AST ≤ 2.5 x the upper limit of normal (ULN).
12. Serum creatinine \< 1.5 x ULN.
13. LDH serum level ≤ 1.5 x ULN.
14. Documented negative test for HIV, HBV and HCV. For HBV serology, the determination of HBsAg and anti-HBcAg Ab is required. In patients with serology documenting previous exposure to HBV (i.e. positive anti-HBsAg with not vaccination and/or positive anti-HBcAg Ab), negative serum HBV-DNA is also required.
15. 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) (v4.03) Grade ≤ 1 unless otherwise specified above.
16. All women of childbearing potential (WOCBP) must have negative pregnancy test results at the screening. WOCBP must be using, from the screening to three months following the last study drug administration, highly effective contraception methods. WOCBP and effective contraception methods are 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, vasectomized partner or sexual abstinence. Pregnancy test will be repeated at the safety visit (only WOCBP and only for patients in Arm 1).
17. 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.
18. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
19. Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
1. Uveal melanoma or mucosal melanoma
2. Evidence of distant metastases at screening.
3. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except: cervical carcinoma in situ, curatively treated basal cell carcinoma, superficial bladder tumors (Ta, Tis \& T1), second primary melanoma in situ or any cancer curatively treated ≥ 5 years prior to study entry.
4. Presence of active infections (e.g. requiring antimicrobial 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.
5. History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
6. Inadequately controlled cardiac arrhythmias including atrial fibrillation.
7. Heart insufficiency (\> Grade II, New York Heart Association (NYHA) criteria).
8. LVEF ≤ 50% and/or abnormalities observed during baseline ECG and Echocardiogram investigations that are considered as clinically significant by the investigator.
9. Uncontrolled hypertension.
10. Ischemic peripheral vascular disease (Grade IIb-IV).
11. Severe diabetic retinopathy.
12. Active autoimmune disease.
13. History of organ allograft or stem cell transplantation.
14. Recovery from major trauma including surgery within 4 weeks prior to enrollment.
15. Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies or any other constituent of the product.
16. Breast feeding female.
17. Anti-tumor therapy (except small surgery) within 4 weeks before enrollment.
18. Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before enrollment.
19. Planned administration of growth factors or immunomodulatory agents within 7 days before enrollment.
20. Patient requiring or taking corticosteroids or other immunosuppressant drugs on a long-term basis will be evaluated case by case with the Sponsor for inclusion/exclusion in the study. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criteria.
21. Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.
22. Previous enrolment and randomization in the same study.

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Study Contact

Sheila Dakhel, PhD

CONTACT

+41 (0) 43 544 88 02

sheila.dakhel@philogen.com

Concetta Aulicino

CONTACT

+39 0577 17 816

regulatory@philogen.com

Study Locations (Sites)

Mayo Clinic Hospital

Phoenix, Arizona, 85054

United States

UC San Diego Moores Cancer Center

La Jolla, California, 92093

United States

UC Irvine Health-Chao Family Comprehensive Cancer Center

Orange, California, 92868-3201

United States

Moffitt Cancer Center

Tampa, Florida, 33612

United States

Winship Cancer Institute, Emory university

Atlanta, Georgia, 30322

United States

Rush University Medical Center

Chicago, Illinois, 60612

United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242

United States

Mayo Clinic

Rochester, Minnesota, 55905

United States

Rutgers Cancer Institute, 195 Little Albany Street

New Brunswick, New Jersey, 08903

United States

Ambulatory Care Center at NYC Langarone Health

New York, New York, 10016

United States

Memorial Sloan Kettering Cancer Center - Main Campus

Ney York, New York, 10065

United States

Duke University Medical Center - Duke Cancer Center

Durham, North Carolina, 27710

United States

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210

United States

St. Luke's Cancer Center, Clinical Trial, 3rd floor, 1600 St. Luke's Blvd.

Easton, Pennsylvania, 18045

United States

Penn State Cancer Institute

Hershey, Pennsylvania, 17033

United States

Fox Chase Cancer Center 333 Cottman Avenue

Philadelphia, Pennsylvania, 19111

United States

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030-4009

United States

Huntsman Cancer Institute, University of Utah 2000 Circle of Hope

Salt Lake City, UT, Utah, 84112

United States

VCU - McGlothlin Medical Education Center

Richmond, Virginia, 980037

United States

Collaborators and Investigators

Sponsor: Philogen S.p.A.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2018-09-20

Study Completion Date2031-12

Study Record Updates

Study Start Date2018-09-20

Study Completion Date2031-12

Terms related to this study

Keywords Provided by Researchers

Melanoma Stage IIIB
Melanoma Stage IIIC
Melanoma Stage IIID

Additional Relevant MeSH Terms

Melanoma Stage IIIB
Melanoma Stage IIIC
Melanoma Stage IIID