The aim of this research is to investigate whether it is feasible and safe to treat operated pancreatic cancer patients who have completed standard of care treatment with dendritic cell immunotherapy using dendritic cells loaded with autologous…
ID
Source
Brief title
Condition
- Exocrine pancreas conditions
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of this project proposal is to determine the feasibility
of administering MesoPher after standard of care adjuvant therapy in patients
with resected pancreatic cancer. We deem this treatment feasible in case 8 out
of 10 patients are able to complete the proposed treatment.
Secondary outcome
As a secondary endpoint we will assess the safety of MesoPher in surgically
resected pancreatic cancer patients.
In addition, we will 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 treatment for individual
patients.
W will also look at efficacy of the treatment.
Background summary
The annual incidence of patients developing pancreatic cancer in the
Netherlands is approximately 3500. In 2030, pancreatic cancer is expected to be
the second leading cause of cancer-related death. The 1-year overall survival
(OS) for pancreatic cancer in the Netherlands is 20%; 5-year OS is only 3%.
Current treatments for pancreatic cancer include cytoreductive surgery, radio-
and chemotherapy. To date, surgical resection is the mainstay of potentially
curative treatment for patients with (borderline) resectable disease. However,
ten years after resection, OS is 4%, demonstrating that cure is exceedingly
rare. Apparently, the vast majority of patients with (borderline) resectable
pancreatic cancer on imaging have occult metastatic disease. In the
Netherlands, almost a third of these patients is found to have more advanced
disease (locally advanced or metastatic) during surgical exploration and
consequently does not undergo a resection. In the end, only 5-25% of all
pancreatic cancer patients are eligible to undergo surgical resection.
We are in need of new treatments in order to curb the progression of pancreatic
cancer. In contrast to radiotherapy and chemotherapy, dendritic cell
vaccination may elicit specific anti-cancer responses without damaging
surrounding healthy tissue and therefore would be a suitable complementary
treatment to the current treatment regime.
While no clinical data is available concerning the efficacy and safety of
allogenic tumor lysate pulsed DC vaccination in patients with pancreatic
cancer, DC therapy with either autologous or allogenic tumor lysate has shown
its feasibility and safety in patients suffering from MM. Here we propose to
use PheraLys, a tumor lysate derived from five different malignant MM cell
lines to load autologous DCs (MesoPher) for patient treatment. Microarray
analysis of these five MM cell lines revealed that PheraLys contains a broad
spectrum (>120) of tumor associated antigens (TAA) and cancer germline antigens
(CGA) which are expected to induce high-avidity T cell responses within the
patients. We argue that MesoPher possesses the potential to induce strong
anti-tumor responses in patients suffering from pancreatic cancer as well,
given the broad overlap of TAA and CGA expression between the two tumor types.
Compared to other cancer types, pancreatic cancer tissue specimens contain a
relatively low number of cancer cells, making autologous tumor lysate for DC
vaccination ineffective. We propose that the use of a lysate derived from five
different MM cell lines to pulse DCs in pancreatic cancer patients has a higher
feasibility than using autologous tumor lysate. Both MM and pancreatic cancer
share multiple, clinically proven TAAs such as but not limited to: WT-1,
mesothelin and MUC-1. In addition, unlike ACT with TCR transduced T cells which
requires patients to have an HLA matching the therapeutic, whole tumor lysate
therapy in the context of DC vaccination is applicable to all patients
regardless of their HLA type.
Recently we found that in a pancreatic cancer mouse model both autologous
dendritic cells loaded with pancreatic cancer lysate as well as autologous
dendritic cells loaded with MM lysate were able to induce a specific immune
response as well as resulting in a significant reduction in tumor growth.
Interestingly there was no significant difference found between both treatment
groups indicating that treating pancreatic cancer patients with autologous
dendritic cells loaded with MM lysate should be feasible.
Therefore, in this study we will primarily investigate whether it is feasible
to use an allogeneic source of tumor antigens from MM cell lines in pancreatic
cancer patients. Our secondary objective is to assess the safety and toxicity
of the treatment as well as the occurrence of anti-tumor/immune responses
within individual pancreatic cancer patients.
Study objective
The aim of this research is to investigate whether it is feasible and safe to
treat operated pancreatic cancer patients who have completed standard of care
treatment with dendritic cell immunotherapy using dendritic cells loaded with
autologous material or peptides. In addition we will investigate efficacy.
Study design
single center open label phase II study.
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 three times every
two weeks. After the third injection with MesoPher, revaccinations to boost the
immune system are given after 3 and 6 months.
Furthermore 3 CT scans will be performed to assess treatment response and
bloodsamples will be collected to monitor the immune system before, during and
after treatment.
Study burden and risks
Patients participating in this study undergo additional outpatient visits and
extra invasive actions in the context of the study. The puncture of a blood
vessel is necessary for leukopheresis, blood sampling and for injection with
the dendritic cells. These invasive actions involve little extra risk.
Leukopheresis is a standard procedure that is performed by qualified personnel
according to a standard protocol. There is a small risk of a short-term
decrease in blood platelets and white blood cells. The leukapheresis can cause
patients to experience transient palpitations, an accelerated heartbeat, a drop
in blood pressure and dizziness. All these complaints are, however, transient.
In addition, there is a very small risk of calcium reduction. If patients
experience these complaints, additional calcium can be given.
The administration of autologous cells that are loaded outside the body with
allogeneic human tumor material poses a potential risk, which is why this risk
is being investigated in this study. Because the lysate itself is not directly
administered to the patient but only when it is processed by the autologous
dendritic cells, we expect that this involves a low risk. Previous clinical
studies showed that injections of tumor lysate-loaded autologous dendritic
cells were generally well tolerated by patients without systemic toxicity.
Exceptions to this were flu symptoms such as fever and shivering.
'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. Patients who did not complete
standard of care due to toxicity or who are not able to start standard of care
due to specific reasons are allowed to participate in the study after approval
of the coordinating investigator.
• Patients who received standard of care post-operative treatment must be
included within six months after completion of treatment. Patients who did not
receive standard of care post-operative treatment must be included within six
months after resection.
• No disease activity as 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) and in
stable medical condition.
• Patients must have normal organ function and adequate bone marrow reserve:
absolute neutrophil count >1.0 x 10E9/l, platelet count > 100 x 10E9/l, and Hb
> 6.0 mmol/l (as determined during screening).
• Women of childbearing potential must have a negative serum pregnancy test at
screening and a negative urine pregnancy test just prior to the first study
drug administration on Day 1, and must be willing to use an effective
contraceptive method (intrauterine devices, hormonal contraceptives,
contraceptive pill, implants, transdermal patches, hormonal vaginal devices,
infusions with prolonged release) or true abstinence (when this is in line with
the preferred and usual lifestyle)* during the study and for at least 12 months
after the last study drug administration.
*True abstinence is acceptable when this is in line with the preferred and
usual lifestyle of the subject. Periodic abstinence (such as calendar,
ovulation, symptothermal, post-ovulation methods) and withdrawal are not
acceptable methods of contraception.
• Men must be willing to use an effective contraceptive method (e.g. condom,
vasectomy) during the study and for at least 12 months after the last study
drug administration.
• Positive DTH skin test (induration > 2mm after 48 hrs) against at least one
positive control antigen tetanus toxoid (see section 8.3 for DTH skin test
procedure).
• 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.
• Current or previous treatment with immunotherapeutic agents.
• Current use of steroids (or other immunosuppressive agents). Patients must
have had 6 weeks of discontinuation and must stop any such treatment during the
time of the study. Prophylactic usage of dexamethasone during chemotherapy is
excluded from this 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 disease
(asthma or COPD), cardiac disease (NYHA class III or IV), 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 keyhole limpet hemocyanin (KLH).
• Pregnant or lactating women.
• Inadequate vein access to perform leukapheresis.
• Concomitant participation in another clinical trial (except participation in
a biobank study).
• An organic brain syndrome or other significant psychiatric abnormality which
would compromise 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
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-003222-92-NL |
| CCMO | NL67169.000.18 |
| Other | NTR NL7674 |
| OMON | NL-OMON28791 |