Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C Melanoma Patients
18 Years and older, Male and Female
PH-L19IL2TNF-01/18 (primary)
NCI-2018-01862
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).
Objectives
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- a2b, 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.
Eligibility
- 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.
Treatment Sites in Georgia
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