The first part of the study will focus on the feasibility of dendritic cell immunotherapy for pancereatic cancer patients.If this treatment is deemed feasible we will investigate immune-response, immune profile, clinical activity and safety and…
ID
Source
Brief title
Condition
- Exocrine pancreas conditions
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the feasibility of the treatment procedure and determine the
establishment of an immune response against mesothelin (TAA*s) in resected
pancreatic cancer patients receiving MesoPher with or without concurrent
low-dose gemcitabine.
Secondary outcome
To determine the systemic immune profile, with emphasis on T lymphocytes, in
surgically resected pancreatic cancer patients; and investigate how these
immune profiles are affected by MesoPher with or without concurrent low-dose
gemcitabine for individual patients.
Study the safety, clinical response and survival of MesoPher with or without
the addition of low-dose chemotherapy in surgically resected pancreatic cancer
patients.
Background summary
Pancreatic cancer is estimated to become the second leading cause of cancer
related mortality by 2020 and the current prognosis of newly diagnosed
pancreatic cancer patient is very poor with a 5-year survival of <5%. We are in
need of new treatment modalities to curb the progression of pancreatic cancer.
Current treatment of pancreatic cancer shows slightly improvement of prognosis.
The introduction of immunotherapy could elicit specific anti-cancer response
without damaging surrounding healthy tissue and therefor would be a great
addition to our current regime. Although preclinical and clinical results of
dendritic cells pulsed with specific tumor antigens and autologous tumor lysate
are very promising, no clinical data is available concerning the efficacy and
safety of allogenic tumor lysate pulsed dendritic cell vaccination in
pancreatic cancer patients.
Study objective
The first part of the study will focus on the feasibility of dendritic cell
immunotherapy for pancereatic cancer patients.
If this treatment is deemed feasible we will investigate immune-response,
immune profile, clinical activity and safety and toxicity of the allogeneic
tumor cell lysate (PheraLys) loaded onto autologous dendritic cells (MesoPher)
with or without a low dose of gemcitabine in resected pancreatic cancer
patients.
Study design
Single center prospective open label Phase I/II study consistuing of 2 parts:
Part 1: feasibility study
Part 2: determine the safety and efficacy of dendritic cell immunotherapy in
combination with a low dose gemcitabine
Intervention
Leukapheresis is performed of which the monocytes are used for differentiation
to dendritic cells using specific cytokines. Pulsed autologous dendritic cells
(MesoPher) are re-injected 3 times every two weeks. After the third injection
with MesoPher, revaccinations to boost the immune system are given after 3 and
6 months.
In the second part of the study MesoPher will be given as described above with
the addition of low-dose gemcitabine.
Study burden and risks
Patients have to undergo extra outdoor visits for this study and extra invasive
procedures especially for this trial, like a catheter in a blood vessel. These
are invasive procedure but risks are limited. This intravenous entrance is
necessary every time, for the leukapheresis, for blood samples and for the
injection of the dendritic cells. A leukapheresis is a standard procedure and
will be performed according to guidelines. There is a limited risk for
transient thrombocytopenia and leukopenia. Adverse events due to administration
of autologous cells, that have been loaded with allogeneic human materials, is
possible but we expect these risks to be limited. Because not the lysate itself
is administered to the patients but only when it is processed by the dendritic
cells of the patient.
's Gravendijkwal 230
Rotterdam 3015 CE
NL
's Gravendijkwal 230
Rotterdam 3015 CE
NL
Listed location countries
Age
Inclusion criteria
* Surgically resected pancreatic cancer
* Completed post-operative standard treatment
* No disease activity assessed by radiological imaging
* 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 0,1, or 2)
* Patients must have normal organ function and adequate bone marrow reserve: absolute neutrophil count > 1.0 x 109/l, platelet count > 100 x 109/l, and Hb > 6.0 mmol/l. (as determined during screening)
* Positive DTH skin test (induration > 2mm after 48 hrs) against at least one positive control antigen tetanus toxoid.
* Ability to return to the hospital for adequate follow-up as required by this protocol.
* Written informed consent according to ICH-GCP
Exclusion criteria
* Medical or psychological impediment to probable compliance with the protocol.
* Previous or current treatment with immunotherapeutic agents..
* Current use of steroids (or other immunosuppressive agents). Patients must have had 6 weeks of discontinuation and must stop of any such treatment during the time of the study. Prophylactic usage of dexamethasone during chemotherapy is excluded from that 6 weeks interval
* Prior 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 patient has been disease-free for five years.
* Serious concomitant disease, or active infections.
* History of autoimmune disease or organ allografts, or with active acute or chronic infection, including HIV and viral hepatitis.
* Serious intercurrent chronic or acute illness such as pulmonary (asthma or COPD) 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 investigational DC treatment.
* Known allergy to shell fish (may contain KLH).
* 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. Lack of availability for follow-up assessment.
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 | EUCTR2017-001135-40-NL |
| CCMO | NL61305.000.17 |