Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C/D Melanoma Patients
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorPhilogen S.p.A.
About this trial
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
This trial does not accept healthy volunteersQualifiers
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).
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.
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.
Males or females, age ≥ 18 years.
Disqualifiers
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, 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.
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Daromun
DrugPatients will receive intratumoral administrations into injectable cutaneous, subcutaneous, and nodal tumors of Daromun once weekly for up to 4 weeks.
Surgery
Procedure/SurgeryPatients will receive surgery.
Adjuvant therapy
DrugPatients will receive adjuvant therapy at the investigator's discretion following the surgery.
Treatment groups
186 Participants
are divided into 2 treatment groupsGroup A: Daromun plus Surgery and Adjuvant therapyExperimental treatment 3 interventions
Group B: Surgery and adjuvant therapyActive comparator 2 interventions
Trial outcomes
Primary outcomes
1
Recurrence Free Survival (RFS)
Recurrence Free Survival (RFS) in a time-to-event analysis in the Daromun plus surgery and adjuvant therapy treatment group (Arm 1) versus the surgery and adjuvant therapy control group (Arm 2). Analysis will be performed for the "Intention To Treat" population.
Time frame
From date of randomization until the date of the first recurrence or date of death from any cause, whichever occurs first assessed up to 60 months.Secondary outcomes
1
Overall survival (OS)
Overall survival (OS) in the Daromun plus surgery and adjuvant therapy treatment group (Arm 1) versus surgery and adjuvant therapy (Arm 2), which will be evaluated in time to event analysis as key secondary endpoint.
Time frame
From date of randomization until the date of the first recurrence or date of death from any cause, whichever occurs first, assessed up to 72 months.2
Recurrence free survival (RFS) as determined by the local investigator
A sensitivity analysis to assess ascertainment bias will be performed on recurrence free survival. For this analysis the primary analysis definition of recurrence will be split into its two components and each will be analyzed separately. The first component/definition will be based on the unblinded assessment performed at the site - any new lesion detected by clinical evaluation which is confirmed by histopathology (biopsy or surgical specimen) and the second component/definition will be based on the assessment of a new lesion detected by allowed imaging modalities in a Blinded Independent Central Review and confirmed, wherever possible, by histological analysis. Each of these components will be analyzed separately using the same statistical model as the primary endpoint. Results from the two component analyses will be compared.
Time frame
From date of randomization until the date of the first recurrence or date of death from any cause, whichever occurs first assessed up to 60 months.3
Event-free survival (EFS)
Event-free survival (EFS) defined as time from randomization to melanoma progression (irresectable stage III or stage IV disease), melanoma recurrence, treatment-related toxicity precluding surgery, treatment-related death, or melanoma-related death, whichever occurs first.
Time frame
From date of randomization until the date of the first event as described above, assessed up to 60 months4
Adverse Events (AE)
Percentage of Patients in Each Treatment Group with AEs, AEs with CTCAE grade ≥3
Time frame
From the inclusion in the study (signature of the informed consent form - ICF) until the first follow-up visit (up to approximately 5 months).Other outcomes
1
Local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS)
Local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) after randomization in the Daromun plus surgery and adjuvant therapy treatment group (Arm 1) versus surgery adjuvant therapy (Arm 2). LRFS is defined as survival free of loco-regional recurrence occurring at any time before systemic recurrence and other events are censored. DMFS is defined as survival free of systemic recurrence, including: 1) systemic recurrence outside the locoregional area at any time before or after locoregional relapse, 2) systemic recurrence with or without loco-regional relapse, or 3) death from cancer with no information on systemic recurrence.
Time frame
From date of randomization until the date of the first recurrence or date of death from any cause, whichever occurs first assessed up to 60 monthsSponsors and contacts
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Source ClinicalTrials.gov