Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C Melanoma Patients (NeoDREAM)

  • STATUS
    Recruiting
  • End date
    Jun 25, 2026
  • participants needed
    186
  • sponsor
    Philogen S.p.A.
Updated on 4 October 2022

Summary

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 melanoma patients with respect to the standard of care (surgery and adjuvant therapy).

Description

The present study is an open-label, randomized, controlled, two-arm multi-center study of the efficacy of Daromun neoadjuvant intratumoral treatment followed by surgery and adjuvant therapy versus surgery and adjuvant therapy in clinical stage III B/C melanoma patients. 186 patients will be randomized in a 1:1 ratio to receive Daromun treatment followed by surgery and adjuvant therapy (Arm 1) or surgery and adjuvant therapy (Arm 2).

In both arms, follow-up for assessing recurrence-free survival will be performed up to five years after randomization. Survival information will also be collected in the following year (up to six years in total after randomization).

This is an open-label study, so there is no blinding.

Patients who successfully complete the screening evaluations and are eligible for participation in the study will be enrolled and randomly assigned (1:1) to two parallel treatment arms: Daromun plus surgery and adjuvant therapy (Arm 1) or surgery and adjuvant therapy (Arm 2).

To ensure a balance across treatment groups, stratified randomization with permuted block will be used and separate randomization list for each subgroup (stratum) will be produced. Patients will be stratified on the basis of the following prognostic factors:

  • Stage of disease (2 levels): Stage IIIB vs. Stage IIIC
  • Planned post-surgical adjuvant therapy (2 levels): anti-PD-1 and other adjuvant therapies.

The primary objective of the study is to demonstrate that a neoadjuvant Daromun treatment followed by surgery and adjuvant therapy improves in a statistically significant manner the recurrence-free survival (RFS) of Stage IIIB/C melanoma patients with respect to the standard of care (surgery and adjuvant therapy).

Primary endpoint of the study is RFS in a time-to-event analysis in the Daromun plus surgery and adjuvant therapy treatment group (Arm 1) versus the surgery plus adjuvant therapy control group (Arm 2). Analysis will be based on the "Intention To Treat" population.

The key secondary objective of the study is to demonstrate that a neoadjuvant Daromun treatment followed by surgery and adjuvant therapy improves in a statistically significant manner the overall survival (OS) of patients with resectable Stage IIIB/ or C melanoma patients with respect to the standard of care (surgery and adjuvant therapy).

For patients enrolled in both arms, local approved post-surgery adjuvant therapies (as part of the standard of care) are allowed and decided at the investigator's discretion. These include high-dose interferon- α2b, anti-CTLA-4 antibodies (e.g. Ipilimumab), anti-PD1 antibodies (e.g. Nivolumab, Pembrolizumab), targeted therapies (e.g. Dabrafenib + Trametinib), or other new local approved treatments.

Details
Condition Melanoma Stage IIIB/C
Treatment adjuvant therapy, Surgery, Daromun
Clinical Study IdentifierNCT03567889
SponsorPhilogen S.p.A.
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Diagnosis of clinical stage IIIB and IIIC (AJCC v7) metastatic melanoma, eligible for complete surgical resection of all metastases (surgically resectable)
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
Males or females, age ≥ 18 years
ECOG Performance Status/WHO Performance Status ≤ 1
Life expectancy of > 24 months
Absolute neutrophil count > 1.5 x 109/L
Hemoglobin > 9.0 g/dL
Platelets > 100 x 109/L
Total bilirubin ≤ 30 µmol/L (or ≤ 2.0 mg/dl)
ALT and AST ≤ 2.5 x the upper limit of normal (ULN)
Serum creatinine < 1.5 x ULN
LDH serum level ≤ 1.5 x ULN
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 negative serum HBV-DNA is also required
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
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)
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
Evidence of a personally signed and dated informed consent document indicating that the subject 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

Exclusion Criteria

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