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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

Phase
Phase 3
Sponsor
Philogen S.p.A.
Enrollment
186
Timeline
Sep 2018 → Dec 2031
About This Study

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).

Eligibility Criteria

Inclusion Criteria

  • 1Histologically 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).
  • 2Eligible 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.
  • 3Prior 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.
  • 4Males or females, age ≥ 18 years.
  • 5ECOG Performance Status/WHO Performance Status ≤ 1.
  • 6Life expectancy of \> 24 months.
  • 7Absolute neutrophil count \> 1.5 x 109/L.
  • 8Hemoglobin \> 9.0 g/dL.
  • 9Platelets \> 100 x 109/L.
  • 10Total bilirubin ≤ 30 μmol/L (or ≤ 2.0 mg/dl).
  • 11ALT and AST ≤ 2.5 x the upper limit of normal (ULN).
  • 12Serum creatinine \< 1.5 x ULN.
  • 13LDH serum level ≤ 1.5 x ULN.
  • 14Documented 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.
  • 15All 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.
  • 16All 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).
  • 17Male 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.
  • 18Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
  • 19Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria

  • 1Uveal melanoma or mucosal melanoma
  • 2Evidence of distant metastases at screening.
  • 3Previous 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.
  • 4Presence 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.
  • 5History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
  • 6Inadequately controlled cardiac arrhythmias including atrial fibrillation.
  • 7Heart insufficiency (\> Grade II, New York Heart Association (NYHA) criteria).
  • 8LVEF ≤ 50% and/or abnormalities observed during baseline ECG and Echocardiogram investigations that are considered as clinically significant by the investigator.
  • 9Uncontrolled hypertension.
  • 10Ischemic peripheral vascular disease (Grade IIb-IV).
  • 11Severe diabetic retinopathy.
  • 12Active autoimmune disease.
  • 13History of organ allograft or stem cell transplantation.
  • 14Recovery from major trauma including surgery within 4 weeks prior to enrollment.
  • 15Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies or any other constituent of the product.
  • 16Breast feeding female.
  • 17Anti-tumor therapy (except small surgery) within 4 weeks before enrollment.
  • 18Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before enrollment.
  • 19Planned administration of growth factors or immunomodulatory agents within 7 days before enrollment.
  • 20Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.
  • 21Previous enrolment and randomization in the same study.

Locations

37 sites participating in this study

Winship Cancer Institute, Emory university

Atlanta, Georgia 30322

Recruiting

Michael Lowe, MD

Mayo Clinic Hospital

Phoenix, Arizona 85054

Recruiting

Mahesh Seetharam, MD

UC San Diego Moores Cancer Center

La Jolla, California 92093

Active, Not Recruiting
Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →