| Eligibility |
Inclusion Criteria:
- written informed consent given, signed and dated
- age = 18 years
- male or female patient with a history of treated metastatic stage IV colorectal or
pancreatic cancer with liver metastases of the primary colorectal or pancreatic cancer
- histologically confirmed primary colorectal or pancreatic cancer
- preferentially with metastatic lesion in the liver amenable to biopsy (must have at
least one measurable lesion or evaluable disease by CT or MRI per RECIST criteria
measured within 56 days prior to trial inclusion)
- expected survival of at least three months
- Karnofsky performance status > 70 %
- patients that have received current standard treatment options (or could not receive
treatment due to medical reasons, e.g. allergic reactions, contraindications,
toxicities etc.) for colorectal cancer (oxaliplatin or irinotecan in combination or
alone with 5-FU with or without treatment combinations of cetuximab and/or bevacizumab
or panitumumab, trifluridine plus tipiracil) or patients with pancreatic cancer that
have received standard treatment options (at least first line therapy, progression or
intolerance to oxaliplatin, irinotecan and 5-FU, FOLFIRINOX as first or second line
therapy) or platinum containing adjuvant chemotherapy and palliative after first line
chemotherapy
- no chemotherapy treatment within the last two weeks (to baseline)
- within the last 2 weeks prior to study day 1 the following laboratory parameters,
which should be within the ranges specified:
Laboratory Parameter Range Absolute neutrophil count (ANC) = 1000/mm3 (= 1.0 x 109/L)
Platelets = 50.000/mm3 (= 80 x 109/L) Creatinine Clearance limit as assessed by GFR > 360
mL/min/1.73m² ALT and AST < 3.0 x ULN (w. liver met.) total bilirubin hemoglobin < 1.5 x
ULN >9 g/dl
- ability to understand character and individual consequences of the clinical trial
- if the patient is female, she must be of non-childbearing potential, or practice
highly effective contraception (Pearl Index <1%, e.g. intrauterine device (IUD)) while
receiving study drug and up to 5 months from the last dose of study drug.
- if the patient is male, he must continue contraception for at least 31 weeks (90 days
plus the time required for nivolumab to undergo 5 half-lives) after the last dose of
investigational drug. In addition, male patients must abstain from sperm donation
during this time
Exclusion Criteria:
Patients presenting with any of the following criteria will not be included in the trial:
- Patients with severe kidney disorders (GFR of <30 mL/min/1.73m² and diagnosed kidney
disease) or who are on hemodialysis.
- The patient requires concomitant chronic treatment with systemic corticosteroids or
any other systemic immunosuppressive agents. Inhaled or topical steroids, and adrenal
replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of
active autoimmune disease (See also Section 7.7)
- Patients taking immunomodulatory medication (e.g. Type 1 interferons).
- Current use of any investigational or non-registered product (drug or vaccine) other
than the study treatment
- Patients with a single metastatic lesion without identified concomitant lymph node
metastasis (i.e. a patient with the intent to resect the metastasis)
- Patients with metastatic colorectal or pancreatic cancer that have a drastic clinical
progression (e.g. from Karnofsky performance 100% to 70%) within the last six weeks
before screening cannot participate
- The patient with active autoimmune disease or with a history of autoimmune disease.
- The patient has a family history of congenital or hereditary immunodeficiency.
- The patient is known to be positive for Human Immunodeficiency Virus (HIV) or other
chronic infections (HBV, HCV) or has another confirmed or suspected immunosuppressive
or immunodeficient condition.
- The patient has concurrent chronic severe medical problems (significant heart failure,
uncontrolled diabetes, bleeding disorder, interstitial lung disease, etc.), unrelated
to the malignancy, that would significantly limit full compliance with the study or
expose the patient to unacceptable risk.
- Patients with untreated known CNS metastases, patients are eligible if CNS metastases
are adequately treated and patients are neurologically returned to baseline (except
for residual signs or symptoms related to the CNS treatment) for at least 2 weeks
prior to trial participation.
- The patient has previous or concomitant malignancies at other sites, except
effectively treated carcinoma in situ of the cervix or effectively treated malignancy
that has been in remission for over 5 years and is highly likely to have been cured.
- For female patients: the patient is pregnant or lactating.
- History of hypersensitivity to the investigational medicinal product or to any drug
with similar chemical structure or to any excipient present in the pharmaceutical form
of the investigational medicinal product
- Known allergy or hypersensitivity to peanuts, soy, soy beans or derivatives of soy or
peanuts
- Contra-indication for MRI
- Participation in another clinical trial within three weeks before screening day
- Patient will not be allowed to enroll in this trial more than once.
- Known microsatellite-instability (MSI-H or dMMR) as evidenced by a standard laboratory
practice (e.g. PCR or staining or sequencing etc.)
- Prisoners or patients who are involuntarily incarcerated.
- Patients who are compulsorily detained for treatment of either a psychiatric or
physical(e.g., infectious disease) illness
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