| Eligibility |
Inclusion Criteria:
- Written informed consent and any locally-required authorization are obtained from the
subject prior to performing any protocol-related procedures, including screening
evaluations
- Male or female > 18 years at time of study entry
- Patients with previously untreated localized T3-T4 N0 or T any or N1-2, M0 rectal
adenocarcinoma requiring preoperative radiotherapy
- Availability of protocol required screening tumor and blood samples
- ECOG performance status of 0 or 1
- Adequate normal organ and marrow function:
1. haemoglobin = 9.0 g/dL, absolute neutrophil count (ANC) = 1.5 x 109/L (> 1500 per
mm3), platelet count = 100 x 109/L (>100,000 per mm3).
2. Serum bilirubin = 1.5 x institutional upper limit of normal (ULN).
3. AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit
4. Serum creatinine CL > 30 mL/min by the Cockcroft-Gault formula (Cockcroft and
Gault 1976) or by 24-hour urine collection for determination of creatinine
clearance
- For women who are not postmenopausal (= 12 months of non-therapy-induced amenorrhea)
or surgically sterile (absence of ovaries and/or uterus): agreement to remain
abstinent (refrain from heterosexual intercourse) or use two adequate methods of
contraception, including at least one method with a failure rate of < 1% per year,
during the treatment period and for at least 6 months after the last dose of
atezolizumab / radio-chemotherapy
- Patients who are not postmenopausal (= 12 months of non-therapy-induced amenorrhea) or
surgically sterile must have a negative serum pregnancy test result within 14 days
prior to initiation of study drug
- Subject is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up.
Exclusion Criteria:
- Patient has locally recurrent or metastatic RC
- Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy,
immunotherapy) or radiotherapy for current rectal cancer disease
- Patients not requiring preoperative radio-chemotherapy
- Participation in another clinical study with an investigational product for any other
indication until 4 weeks before study participation
- Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,
endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal
antibodies, other investigational agent) = 21 days prior to the first dose of study
drug
- Any previous treatment with a PD1 or PD-L1 inhibitor, including atezolizumab
- History of another primary malignancy except for:
1. Malignancy treated with curative intent and with no known active disease =5 years
before the first dose of study drug and of low potential risk for recurrence
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease
3. Adequately treated carcinoma in situ without evidence of disease e.g., cervical
cancer in situ
- Any prior Grade =3 immune-related adverse event (irAE) while receiving any previous
immunotherapy agent, or any unresolved irAE >Grade 1
- Current or prior use of immunosuppressive medication within 28 days before the first
dose of atezolizumab, with the exceptions of intranasal and inhaled corticosteroids or
systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of
prednisone, or an equivalent corticosteroid
- Treatment with systemic immunostimulatory agents (including but not limited to
interferons or IL-2) within 4 weeks or five half-lives of the drug (whichever is
shorter) prior to randomization
- Receipt of live attenuated vaccination within 30 days prior first atezolizumab planned
administration (i.e. at week 3 after study entry) or within 5 months of receiving
atezolizumab or anticipation that such a live attenuated vaccine will be required
during the study. Influenza vaccination (inactivated forms only but not live
attenuated forms) should be given during influenza season only (approximately October
to March).
- Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3
electrocardiograms (ECGs) using Frediricia's Correction
- Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects
with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within
the past 2 years) are not excluded. Patients with a history of autoimmune-related
hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for
this study. Patients with controlled Type 1 diabetes mellitus on a stable insulin
regimen may be eligible for this study
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
ulcerative colitis)
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan
- History of primary immunodeficiency
- History of allogeneic organ transplant
- History of hypersensitivity to atezolizumab or any excipient
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
bleeding diatheses, any subject known to have evidence of acute or chronic hepatitis
B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social
situations that would limit compliance with study requirements or compromise the
ability of the subject to give written informed consent
- Subjects with uncontrolled seizures.
- Known history of active tuberculosis
- Female subjects who are pregnant, breast-feeding or female patients of reproductive
potential who are not employing or willing to employ an effective method of birth
control
- Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results
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