Cryotherapy With in Situ Immunotherapy in Melanoma Metastasis
Status:
Active, not recruiting
Trial end date:
2022-10-01
Target enrollment:
Participant gender:
Summary
Melanoma is the deadliest form of skin cancer and its incidence has doubled every 20 years in
France, where this cancer is responsible of more than 1600 deaths each year.
Patients with early diagnosis have good prognosis and can be generally cured by surgery only.
Advanced melanoma however has a very bad prognosis.
Loco-regional lymph nodes are usually the first distant localization in metastatic melanoma.
Lymph node dissection is then the recommended treatment, although it's impact on survival has
never been proven.
In the same way, the benefit risk profile of interferon as adjuvant treatment after lymph
node dissection is still much debated.
Recently, new treatments either with immunotherapy (ipilimumab, nivolumab) or by the targeted
therapy dabrafenib/trametinib in patients with BRAF mutation have shown an impact on survival
in the adjuvant setting after lymph node dissection.
But, it has not yet been established if this strategy has a benefit gain compared to starting
those treatments only in the metastatic setting after watchful follow-up.
Moreover, if these novel therapies (targeted therapies: TT, immunotherapies : IT)
demonstrated for the first time a real benefit in terms of survival or of responses rates in
melanoma, physicians and patients had to address new problems, such as the management of
unusual adverse events.
Partial and dissociated responses can also be seen with those new treatments. Some patients
will have complete response in some lesions, stabilization in others and progression in a
few. It is to be expected that one of the real key points of this therapy is to be found
here, as this situation is commonly seen, and it would probably be a poor choice to stop a
treatment that is globally effective for progression of only 1 or 2 lesions, in a patient
otherwise stabilized.
That is the context in which interventional radiology (IR) should be considered as an
extremely efficient option. IR is a real medical revolution in the last 2 decades.
It provides not only the opportunity to determine the characteristics of residual lesion
(fibrosis, necrosis, metastasis, or sarcoidosis,…) by biopsy, but allows also their targeted
destruction through different technics (cryotherapy, radiofrequency, laser,…).
The investigators are fortunate to have in their institution one of the best IR department of
the world (headed by Prof. Afshin GANGI), with a technical platform unique in Europe that
allows IR through ultrasound, scan, petscan and MRI.
To the best of their knowledge, Immunotherapy associated with IR has not been performed so
far.
This association could in theory:
1. Combine immunotherapy with tumoral necrosis, which inherently increases the effects of
immunotherapy by massive tumoral leakage of danger signals and tumoral antigens;
2. Allow direct injection in targeted zones, where the beneficial effect is desired, and
thus increase the expected immune response;
3. Reduce side effects related to immunotherapy, by reducing quantities injected; which
seems particularly important in the (neo)-adjuvant setting.
That's why the investigators are willing to conduct this pilot project, the objectives of
which are:
1. Providing a proof of the feasibility of this association,
2. Obtaining preliminary insights on the effects on non-targeted lesions,
3. Adding a translational research to establish the effect on tumor antigenic expression
and the immune response.