| Eligibility |
Inclusion Criteria:
- Male and female patients with histologically confirmed diagnosis of rectal
adenocarcinoma localized 0 - 12 cm from the anocutaneous line as measured by rigid
rectoscopy (i.e. lower and middle third of the rectum)
- Staging requirements: High-resolution, thin-sliced (i.e. 3 mm) magnetic resonance
imaging (MRI) of the pelvis is the mandatory local staging procedure.
- Patients with MRI-defined low risk rectal cancer with the presence of at least one of
the following conditions:
- cT2N0 or cT3a/bN0 tumors =6 cm from the anocutaneous line that would require
abdominoperineal resection or permanent colostomy
- Any rectal cancer of the upper third (12-16 cm) requiring FU-CRT according to
German S3 guideline recommendations (i.e. cT4, mrCRM+, extensive N+)
- Patients with MRI-defined intermediate/high risk rectal cancer, but not eligible for
TNT (oxaliplatin-containing) protocols:
- any cT3 if the distal extent of the tumor is < 6 cm from the anocutaneous line,
or
- cT3c/d in the middle third of the rectum (= 6-12 cm) with MRI evidence of
extramural tumor spread into the mesorectal fat of more than 5 mm (>cT3b), or
- cT3 with clear cN1 based on strict MRI-criteria (see appendix)
- cT4 tumors, or
- Tany middle/low third of rectum with clear MRI criteria for N2
- mrCRM+ (= 1mm), or
- Extramural venous invasion (EMVI+)
- Trans-rectal endoscopic ultrasound (EUS) is additionally used when MRI is not
definitive to exclude early cT1 disease in the lower third or middle third of the
rectum.
- Spiral-CT of the abdomen and chest to exclude distant metastases.
- Aged at least 18 years. No upper age limit
- WHO/ECOG Performance Status =1
- Adequate hematological, hepatic, renal and metabolic function parameters:
- Leukocytes = 3.000/mm^3, ANC = 1.500/mm^3, platelets = 100.000/mm^3, Hb > 9 g/dl
- Serum creatinine = 1.5 x upper limit of normal
- Bilirubin = 2.0 mg/dl, SGOT-SGPT, and AP = 3 x upper limit of normal
- Informed consent of the patient
Exclusion Criteria:
- Distant metastases (to be excluded by CT scan of the thorax and abdomen)
- Prior antineoplastic therapy for rectal cancer
- Prior radiotherapy of the pelvic region
- Major surgery within the last 4 weeks prior to inclusion
- Subject pregnant or breast feeding, or planning to become pregnant within 6 months
after the end of treatment.
- Subject (male or female) is not willing to use highly effective methods of
contraception during treatment and for 6 months after the end of treatment.
- On-treatment participation in a clinical study in the period 30 days prior to
inclusion
- Previous or current drug abuse
- Other concomitant antineoplastic therapy
- Serious concurrent diseases, including neurologic or psychiatric disorders (incl.
dementia and uncontrolled seizures), active, uncontrolled infections, active,
disseminated coagulation disorder
- Clinically significant cardiovascular disease in (incl. myocardial infarction,
unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac
arrhythmia) = 6 months before enrolment
- Prior or concurrent malignancy = 3 years prior to enrolment in study (Exception:
non-melanoma skin cancer or cervical carcinoma FIGO stage 0-1), if the patient is
continuously disease-free
- Known allergic reactions on study medication
- Known dihydropyrimidine dehydrogenase deficiency
- Psychological, familial, sociological or geographical condition potentially hampering
compliance with the study protocol and follow-up schedule (these conditions should be
discussed with the patient before registration in the trial).
- History of severe hepatic impairment (e.g. Child-Pugh = Grade C)
- Moderate (Creatinine Clearance 30 to 49 mL/minute), severe (Creatinine Clearance <30
mL/minute) renal impairment
- Neutropenia (neutrophil count <1.5x109/l)
- Known hypersensitivity to Anakinra or E. coli derived proteins, Anakinra or any of the
components of the product
- Asthma
- Patients with clinically significant bacterial, fungal, parasitic or viral infection,
which require acute therapy. Patients with acute bacterial infections requiring
antibiotic use should delay screening/enrollment until the course of antibiotic
therapy has been completed
- Patients with known active hepatitis B, C or who are HIV-positive or who are at risk
for HBV reactivation. At risk for HBV reactivation is defined as hepatitis B surface
antigen positive or anti-hepatitis B core antibody positive. Prior test results
obtained as part of standard of care that confirm a subject is immune and not at risk
for reactivation (ie, hepatitis B surface antigen negative, surface antibody positive)
may be used for purposes of eligibility and tests do not need to be repeated. Subjects
with prior positive serology results must have negative polymerase chain reaction
results. Subjects whose immune status is unknown or uncertain must have results
confirming immune status before enrollment.
- Subjects who are already using the following medications will not be allowed:
- Tumor necrosis alpha inhibitors: Use on any of these biologics within 8 weeks of
screening or baseline visit.
- IL-6 inhibitors: Use of any IL-6 inhibitors within 8 weeks of screening or
baseline visit
- Janus Kinase inhibitors: Use of baricitinib, tofacinitib, upadacitinib, and
ruxolitinib, oclacitinib, fedratinib, within 2 weeks from screening or baseline
visit.
- Bruton's tyrosine kinase inhibitors: Ibrutinib, acalabrutinib, zanubrutinib
- CCR5 antagonist (CCR5 = C-C Chemokine Receptor Type 5; DMARD = Disease Modifying
Anti-Rheumatic Drug): Leronlimab is also an immunomodulator.
- DMARDs: cyclosporine, cyclophosphamide, mycophenolic acid, chlorambucil,
penicillamine, azathioprine: Use within 6 months prior to screening or baseline
visit.
- Rituximab: Use of rituximab within 1 year of screening or baseline visit.
- Abatacept: Use of abatacept within 8 weeks of screening or baseline visit.
- Patients who have any severe and/or uncontrolled medical conditions or other
conditions that could affect their participation such as severe impaired lung
functions as defined as spirometry and DLCO that is 50% of the normal predicted value
and/or O2 saturation that is 88% or less at rest on room air
- Patients under ongoing treatment with another investigational medication or having
been treated with an investigational medication within 30 days (incl. live attenuated
vaccine) of screening or 5 half-lives (whichever is longer) prior to the first dose of
investigational product
- Patients receiving chronic, systemic treatment with corticosteroids or another
immunosuppressive agent. Topical or inhaled corticosteroids are allowed
- History of any other disease, physical examination finding, or clinical laboratory
finding giving reasonable suspicion of a disease or condition that contraindicates use
of an investigational drug, or that might affect interpretation of the results of this
study, or render the subject at high risk for treatment complications.
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