This phase I/II study consists of 2 subsequent study parts. In the phase I part we will investigate the safety of combining IMM-101 administration with SBRT in 20 patients with locally advanced pancreatic cancer who have completed at least 4 cycles…
ID
Source
Brief title
Condition
- Exocrine pancreas conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
For the first phase of 20 patients, safety defined as max 6 out of 20 patients
experiencing a grade 4/5 toxicity related to the IMM-101 intervention, will be
the main endpoint. Safety evaluation will take place after the 20th patients
has received the 3rd vaccination. For the overall study efficacy, defined as an
increase of 20% in 1-year progression free survival, will be the main endpoint.
Secondary outcome
Secondary endpoints for the overall study will be overall survival, time to
locoregional progression, time to distant metastasis, safety/toxicity,
feasibility, resection rate, immune responses and quality of life/sleep.
Background summary
Approximately 30-40% of patients with pancreatic cancer present with locally
advanced disease. Patients with locally advanced pancreatic cancer cannot be
surgically resected but at the same time have no clinically detectable distant
metastasis. Current treatment regimens consist of neoadjuvant chemotherapy with
FOLFIRINOX, followed by stereotactic body radiation therapy. Despite slow
improvements in patient outcomes, this strategy results in only approximately a
third of patients being surgically resectable and an overall survival of only
10-12 months due to the development of metastatic disease. Recently, improved
understanding in the field of tumor immunology has led to progress and
breakthroughs in cancer immunotherapeutic strategies. One such therapeutic
strategy is immunotherapy using modulators of the immune system. Radiation
therapy can act as an in-situ vaccine, increasing the expression of cell
surface receptors and tumor antigen presentation and can even produce
anti-tumor cytotoxic T cell response. However, optimal anti-tumor response
requires an intact host*s immune system and without amplification, the
anti-tumor immunity arising from radiation therapy is likely to be limited. It
is hypothesized that the combination of boosting the immune responses in the
presence of an increased exposure to tumor antigen will provide sufficient
induction of the immune system to counter further tumor growth. IMM-101,
through its activation and maturation of antigen presenting cells. Especially
dendritic cells can aid in the antigen processing and T-cell cross priming,
processes that are deficient in the setting of advanced pancreatic cancer.
IMM-101 immunotherapy thereby has the potential to optimize the immunogenic
anti-tumor effect of radiation therapy.
Study objective
This phase I/II study consists of 2 subsequent study parts. In the phase I part
we will investigate the safety of combining IMM-101 administration with SBRT in
20 patients with locally advanced pancreatic cancer who have completed at least
4 cycles of FOLFIRINOX chemotherapy. If deemed safe and feasible (safety
evaluation will take place after the 20th patient has received the 3rd
vaccination and safety will be defined as max 6 out of 20 patients experiencing
a grade 4/5 toxicity related to the IMM-101 intervention) we will continue
inclusion in the next pahse of the study with the inclusion of an additional 18
patients in order to be able to study efficacy of combining IMM-101 treatment
with SBRT based on a 20% improvement of 1-year disease free survival. Secondary
endpoints will be overall survival, time to locoregional progression, time to
distant metastasis, feasibility, safety/toxicity, resection rate, tumor
specific immune-responses and quality of life/sleep.
Study design
An open-label, non-randomized phase I/II single-center study.
Intervention
Six intradermal injections of IMM-101 (a vaccine adjuvant containing
Heat-Killed Whole Cell Mycobacterium obuense) beginning 2 weeks prior to
stereotactic body radiation therapy. Between the third and fourth injection
will be a four-week break. Administration of IMM-101 will be performed at week
0,2,4,8,10 and 12.
Study burden and risks
Patients will receive six intradermal injections with IMM-101 during a 12-week
period. In addition, they will undergo additional blood collections for
determining tumor-specific immune responses. These blood collections can cause
bruising or slight short-term discomfort. Furthermore, patients will be
instructed to wear an Actiwatch during two 7-day periods to determine their
activity level during daytime and duration of sleep during the night. In
addition, they will be asked to complete questionnaires for quality of life (3
visits) and sleep (2 visits) during the study period. Apart from the time
needed to complete these questionnaires no extra burden will be expected from
these quality of life/sleep measurements.
In previously performed trials, IMM-101 administration proved to be safe
showing a low toxicity profile. The main adverse reactions were limited to
local skin reactions so we do not expect any major side-effects of this
treatment in our patient population. However, since IMM-101 is composed of
foreign material, not all reactions can be excluded and thus some uncertainty
as to the safety of the product exists. Therefore, we will first include a
limited number of patients (n=20) in a phase I study in order to establish
safety and feasibility of IMM-101 administration before we will enroll more
patients (n=18) in the subsequent phase II part of the trial.
Since locally advanced pancreatic cancer is a deadly disease with an extremely
poor survival rate we find that the above-mentioned risks and burden do not
outweigh the potential benefit for patients participating in this trial. The
study has been designed to test the safety and feasibility of administration of
the IMM-101 product, before a subsequent phase II study assessing safety and
efficacy is undertaken. In this way we limit any unwanted adverse effects or
lack of efficacy to as few patients as possible.
's-Gravendijkwal 230
Rotterdam 3015 CE
NL
's-Gravendijkwal 230
Rotterdam 3015 CE
NL
Listed location countries
Age
Inclusion criteria
• Histologically confirmed pancreatic cancer, as indicated by a definite
cytology report
• Tumor considered locally advanced after diagnostic work-up including
CT-imaging and diagnostic laparoscopy.
• Age > 18 years and < 75 years.
• WHO performance status of 0 or 1.
• ASA classification I or II.
• No evidence of metastatic disease.
• Largest tumor diameter < 7 cm x 7 cm x 7 cm.
• No direct tumor involvement oft he stomach, colon or small bowel.
• Normal renal function (Creatinine >= 30 ml/min).
• Normal liver tests (bilirubin < 1.5 times normal; ALAT/ASAT < 5 times normal).
• Normal bone marrow function (WBC > 3.0 x 10e9/L, platelets > 100 x 10e9/L and
hemoglobin > 5.6 mmol/l).
• Ability to wear and Actiwatch device on non-dominant arm
• Written informed consent.
Exclusion criteria
• Previous allergic reaction to any mycobacterial product
• Prolonged systemic corticosteroid or immunosuppressant medication use
• Pregnancy
• Lymph node metastases from primary tumor outside the field of radiation.
• Second primary malignancy except in situ carcinoma of the cervix, adequately
treated non-melanoma skin cancer, or other malignancy treated at least 3 years
previously without evidence of recurrence.
• Pregnancy, breast feeding.
• Serious concomitant systemic disorders that would compromise the safety of
the patient or his/her ability to complete the study, at the discretion of the
investigator.
• An active autoimmune disease that has required systemic treatment in past 2
years (i.e. with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment.
• Diagnosis of immunodeficiency or receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the planned
first dose of the study. The use of physiologic doses of corticosteroids may be
approved after consultation with the Sponsor.
• Known history of Human Immunodeficiency Virus (HIV) (HIV-1/2 antibodies).
• Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
• Live virus vaccine within 30 days of planned start of trial treatment.
• Use of herbal remedies, including traditional Chinese herbal products (e.g.,
mistletoe).
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 | EUCTR2019-000216-29-NL |
| CCMO | NL68762.078.19 |
| Other | NTR NL7578 |
| OMON | NL-OMON22166 |