To assess the feasibility of administering DCBI after CRS-HIPEC in patients with malignant peritoneal mesothelioma.
ID
Source
Brief title
Condition
- Mesotheliomas
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The aim of this phase II study is to determine the feasibility of adjuvant DCBI
with injection of MesoPher in patients with MPM after CRS-HIPEC.
Secondary outcome
Secondary endpoint of this study is safety of this therapy, which has already
been proven in patients with pleural mesothelioma. Another secondary endpoint
is the determination of an immunological response against the tumor as result
of the adjuvant therapy.
Background summary
Malignant peritoneal mesothelioma (MPM) is an uncommon but aggressive neoplasm,
related to asbestos exposure. MPM has low survival rates of approximately one
year, even after palliative surgery and/or systemic chemotherapy. Recent
advancement in treatment strategies that focus on cytoreductive surgery (CRS)
and hyperthermic intraperitoneal chemotherapy (HIPEC) have resulted in improved
median survival of 53 months and a 5-year survival of nearly 50%. However,
recurrence rates are high. Current systemic chemotherapy in the adjuvant
setting is of limited efficacy, while immunotherapy with dendritic cell based
immunotherapy (DCBI) has yielded promising results in murine models with
peritoneal mesothelioma and in patients with pleural mesothelioma.
Study objective
To assess the feasibility of administering DCBI after CRS-HIPEC in patients
with malignant peritoneal mesothelioma.
Study design
An open-label single-centre phase II study.
Intervention
4 to 6 weeks before CRS-HIPEC a leukapheresis is performed of which the
monocytes are used for differentiation to dendritic cells (DCs) using specific
cytokines. Pulsed autologous DCs (MesoPher) are re-injected 8-10 weeks after
surgery, 3 times every two weeks. After the third injection with MesoPher,
revaccinations to boost the immune system are given after 3 and 6 months.
Study burden and risks
Patients have to undergo extra outpatient visits for this study and extra
invasive procedures especially for this trial, like an intravenous catheter.
These are invasive procedures but risks are limited. This IV entrance is
necessary, for the leukapheresis, for blood samples and for the injection of
the DCs. A leukapheresis is a standard procedure and will be performed
according to standard procedures. There is a limited risk for transient
thrombocytopenia and leukopenia. During the leukapheresis patients can
experience palpitations, increased heartrate, a decrease in blood pressure and
dizziness. All of these complaints are transient. In addition, there is a low
risk of a calcium reduction. If patients experience complaints, extra calcium
may be administered to the patient.
The administration of autologous cells, that have been loaded with allogeneic
human materials, is a potential risk and that is one subject of the study.
Because not the lysate itself is administered to the patients but only when it
is processed by the dendritic cells of the patient we expect these risks to be
limited. Pervious clinical studies showed that injection with tumor
lysate-pulsed autologous DCs was overall well tolerated without systemic
toxicity, with the exception of a low-grade flu-like symptoms like fever and
rigors.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
• Patients with a histologically confirmed diagnosis of malignant peritoneal
mesothelioma
• Patients must be at least 18 years old and must be able to give written
informed consent
• Patients must be ambulatory (WHO-ECOG performance status 0 or 1) and in
stable medical condition
• Patients must have normal organ function and adequate bone marrow reserve:
absolute neutrophil count >1.0 *109/l, platelet count >100*109/l and Hb
>6.0mmol/l
• Ability to return to the study center for adequate follow-up and vaccinations
• Positive DTH skin test (induration > 2mm after 48 hrs) against at least
one positive control antigen tetanus toxoid.
• Written informed consent according to the ICH-GCP
• Planned start date of vaccination within 8-10 weeks after CRS-HIPEC
• The expected survival must be at least 6 months
• Ability to return to the Erasmus MC for adequate follow-up as required by
this protocol
Exclusion criteria
4.3 Exclusion criteria A potential participant who meets any of the following
criteria will be excluded from participation in the study: • Extra-abdominal
disease/ metastatic disease • Medical or psychological impediment to probable
compliance with the protocol • Current use of steroids or other
immunosuppressive agents. Patients must have had six weeks of discontinuation
before the first vaccination and must stop any such treatment during the time
of the study on the basis of potential immune suppression. Prophylactic usage
of dexamethasone during chemotherapy is excluded from that 6 weeks interval. •
Prior cytoreductive surgery • 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 or a malignancy that requires no active
treatment. • Serious concomitant disease or active infections • History of
auto-immune disease or organ allografts, or with active or chronic infection,
including HIV and viral hepatitis • 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 CRS-HIPEC or investigational DC
treatment • Pregnant or lactating women • Inadequate peripheral vein access to
perform leukapheresis • Concomitant participation in another clinical trial •
An organic brain syndrome or other significant psychiatric abnormality which
would comprise the ability to give informed consent, and preclude participation
in the full protocol and follow-up • Absence of assurance of compliance with
the protocol • Patients with a known allergy to shell fish (may contain KLH)
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 |
|---|---|
| EudraCT | EUCTR2017-000897-12-NL |
| ClinicalTrials.gov | NCT02395679 |
| CCMO | NL60856.000.17 |