This study has been transitioned to CTIS with ID 2024-514054-70-00 check the CTIS register for the current data. To assess whether (neo)-adjuvant DCT in combination with eP/D is feasible in early stage epithelioid MPM patients after first-line…
ID
Source
Brief title
Condition
- Mesotheliomas
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the feasibility of DCT performed before and after eP/D in patients
with early stage epithelioid MPM who received first line chemotherapy.
Secondary outcome
To assess the safety of DCT performed before and after eP/D in patients with
early stage epithelioid MPM.
To evaluate the efficacy (as measured by progression free and overall survival)
of combining DCT and eP/D after chemotherapy in patients with early stage
epithelioid MPM.
To determine the anti-tumor immune response induced by (neo)adjuvant DCT.
Background summary
Malignant pleural mesothelioma (MPM) is an uncommon but aggressive neoplasm
with low survival rates. So far, standard-of-care treatment for MPM is
antifolate/platinum-based chemotherapy. For patients with early stage MPM the
role of radical surgery remains controversial and multimodal treatment might
improve patients* prognosis. Dendritic cell therapy (DCT), Mesopher, proved to
be safe and yielded promising results in patients with MPM. On one hand, DCT
showed ability to reduce tumor load in some patients; on the other hand, it
demonstrated a better outcome when injected earlier in tumor development in
preclinical models, thus representing the rationale for a combined
(neo)adjuvant approach with extended pleurectomy/decortication (eP/D) surgery.
Study objective
This study has been transitioned to CTIS with ID 2024-514054-70-00 check the CTIS register for the current data.
To assess whether (neo)-adjuvant DCT in combination with eP/D is feasible in
early stage epithelioid MPM patients after first-line chemotherapy.
Study design
This is an open label, single center, phase 1 study.
Intervention
Before standard-of-care chemotherapy, a leukapheresis will be performed and
monocytes will be collected for the production of DCT. Allogeneic tumor lysate
(Pheralys) loaded autologous DCs (MesoPher) will be re-injected 4 weeks (+/- 1
week) after completing chemotherapy, 2 times every other week. Four weeks after
the first injection with DCT, patients will undergo eP/D surgery and receive
three bi-weekly injections with DCT (starting 4 weeks after surgery).
Study burden and risks
Patients have to undergo extra outpatient visits and blood tests for this
trial. The last one is an invasive procedure, but risks are limited. A
non-mandatory biopsy will be collected before starting neo-adjuvant DCT. This
will be either a computerized tomography (CT)-guided needle biopsy or a
Video-Assisted Thoracoscopic Surgery (VATS) surgical biopsy. Some possible
complications may include, but are not limited to pneumothorax, bleeding in the
lung and infection. An intravenous entrance is necessary for the leukapheresis,
for blood samples and for the injection of MesoPher. Leukapheresis is a
standard procedure and will be performed according to standard procedures.
There is a limited risk for transient thrombocytopenia and leukopenia. DCT with
Mesopher (autologous DCs loaded with Pheralys) already proved to be safe in
patients with MPM. Possible side effects are described within the protocol.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
• Patients with a histologically confirmed diagnosis of epithelioid MPM who are
eligible for 2 to 4 cycles of platinum-based chemotherapy.
• Patients must be at least 18 years old and must be able to give written
informed consent.
• ECOG performance status 0-1.
• Written informed consent according to ICH-GCP.
•Fit to receive platinum-based chemotherapy (as per standard of care of the
treating
physician/Institution) and undergo a P/D with optional removal of hemidiaphragm
and
pericardium. The responsible surgeon and chest physician should judge the
required
fitness prior to registration, taking into account the results of all the
relevant (i.e. pulmonary,
cardiac) examinations.
• Tumor tissue available after completing chemotherapy and before starting
treatment with DCT. Tumor tissue can be obtained by either a CT-guided needle
biopsy or a VATS surgical biopsy.
Exclusion criteria
• Clinical or radiological invasion of mediastinal structures (heart, aorta,
spine, esophagus,
etc.) and widespread chest wall invasion (stage T4). Involvement of
supraclavicular
or coeliac nodes. Stage IV (metastatic disease).
• Subject with any concurrent medical, psychological or psychiatric disease or
condition
that is likely to compromise the ability to give informed consent or to
interfere
with study procedures or results, or that in the opinion of the investigator
would constitute
a hazard for participating in this study.
• Subject with any previous malignancy except adequately treated basal cell or
squamous
cell skin cancer, superficial or in-situ cancer of the bladder or other cancer
for
which the subject has been disease-free for at least 3 years.
• Subject with any known active serious infection, including human
immunodeficiency
virus (HIV), hepatitis B or C virus, or syphilis infection.
• Subject with a history of autoimmune disease, except for diabetes mellitus
type I or
other conditions, where patient can be eligible following discussion with
medical
monitor.
• Subject who has received an organ allograft.
• Serious intercurrent chronic or acute illness such as pulmonary (COPD or
asthma)
or cardiac (NYHA class III or IV) or hepatic disease or other illness
considered by
the study coordinator to constitute an unwarranted high risk for eP/D or
investigational
DCT.
•Unavailability of tumor tissue after completing chemotherapy and before
starting treatment with DCT.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-514054-70-00 |
| EudraCT | EUCTR2021-000496-37-NL |
| CCMO | NL76712.000.21 |