Gender
All
Age Group
12 Years and up
Accepting Healthy Volunteers
No
Inclusion Criteria:
- Histologically proven stage III colon adenocarcinoma (any T [Tx, T1, T2, T3, or T4],
N1-2M0; includes N1C); tumors must be deemed to originate in the colon including
tumors that extend into/involve the small bowel (e.g. those at the ileocecal valve)
- Presence of deficient (d) DNA mismatch repair (dMMR); MMR status must be assessed by
immunohistochemistry (IHC) for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where
loss of one or more proteins indicates dMMR; dMMR may be determined either locally
or by site-selected reference lab; Note: loss of MLH1 and PMS2 commonly occur
together; formalin-fixed paraffin-embedded (FFPE) tumor tissue is required for
subsequent retrospective central confirmation of dMMR status
- Patients who are known to have Lynch syndrome, have been found to carry a specific
germline mutation in an MMR gene (MLH1, MSH2, MSH6, PMS2), and have been shown to be
dMMR by IHC are eligible to participate
- Tumors must have been completely resected; in patients with tumor adherent to
adjacent structures, en bloc R0 resection must be documented in the operative report
or otherwise confirmed by the surgeon; near or positive radial margins are
acceptable so long as en bloc resection was performed; proximal or distal margin
positivity is not permitted
- Entire tumor must be in the colon (rectal involvement is an exclusion); surgeon
confirmation that entire tumor was located in the colon is required only in cases
where it is important to establish if the tumor is a colon versus (vs.) rectal
primary; patients with more than one primary colon adenocarcinoma are eligible if
the qualifying stage III tumor is confined to the colon, and not rectum, and the
other cancers of lower stage are removed in the en bloc R0 resection
- Based upon the operative report and other source documentation, the location of the
primary tumor will be categorized as proximal or distal to the splenic flexure
(included with distal), and further categorization will be as follows:
cecum/ascending, transverse, descending, sigmoid colon, or rectosigmoid colon
- No evidence of residual involved lymph node disease or metastatic disease at the
time of registration based on clinician assessment of imaging; the treating
physician will determine if incidental lesions on imaging require workup to exclude
metastatic disease; if based on review of images, the treating physician determines
the patient to be stage III, then the patient is eligible
- No prior medical therapy (chemotherapy, immunotherapy, biologic or targeted therapy)
or radiation therapy for the current colon cancer except for one cycle of mFOLFOX6
- Age >= 12 years
- Performance Status:
- Patients < 16 years of age: Lansky >= 50%
- Patients 16 to < 18 years of age: Karnofsky >= 50%
- Patients >= 18 years of age: Eastern Cooperative Oncology Group (ECOG)
performance status =< 2
- This study involves: 1) an investigational agent whose genotoxic, mutagenic and
teratogenic effects on the developing fetus and newborn are unknown; and 2) an agent
that has known genotoxic, mutagenic, and teratogenic effects; therefore, for women
of childbearing potential only, a negative pregnancy test done =< 7 days prior to
registration is required; a female of childbearing potential is a sexually mature
female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has
not been naturally postmenopausal for at least 12 consecutive months (i.e. has had
menses at any time in the preceding 12 consecutive months)
- Absolute neutrophil count (ANC) >= 1500 mm^3
- Platelet count >= 100,000 mm^3; platelets >= 75,000 required for patients who
received cycle 1 of mFOLFOX6 prior to registration
- Creatinine =< 1.5 x upper limit of normal (ULN) or
- Calculated creatinine clearance >= 45 mL/min by Cockcroft-Gault equation
- Alternatively, for patients < 18 years of age, maximum serum creatinine =< the
below age-gender-specific norms:
- 12 years: 1.2 (male and female)
- 13 to < 16 years: 1.5 (male), 1.4 (female)
- 16 to < 18 years: 1.7 (male), 1.4 (female)
- Total bilirubin =< 1.5 x upper limit of normal (ULN) except in the case of Gilbert
disease
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit
of normal (ULN)
- Thyroid-stimulating hormone (TSH) within normal limits (WNL); supplementation is
acceptable to achieve a TSH WNL; in patients with abnormal TSH, if free T4 is normal
and patient is clinically euthyroid, patient is eligible
- No active known autoimmune disease, including colitis, inflammatory bowel disease
(i.e. ulcerative colitis or Crohn's disease), rheumatoid arthritis,
panhypopituitarism, adrenal insufficiency
- No known active hepatitis B or C
- Active hepatitis B can be defined as:
- Hepatitis B virus surface antigen (HBsAg) detectable for > 6 months;
- Serum hepatitis B virus (HBV) DNA 20,000 IU/ml (105 copies/ml); lower
values 2,000-20,000 IU/ml (104-105 copies/ml) are often seen in hepatitis
B virus e antigen (HBeAg)-negative chronic hepatitis B
- Persistent or intermittent elevation in ALT/AST levels
- Liver biopsy showing chronic hepatitis with moderate or severe
necroinflammation
- Active hepatitis C can be defined as:
- Hepatitis C antibody (AB) positive AND
- Presence of hepatitis C virus (HCV) RNA
- No grade >= 2 peripheral motor or sensory neuropathy
- Patients positive for human immunodeficiency virus (HIV) are eligible only if they
meet all of the following:
- A stable regimen of highly active anti-retroviral therapy (HAART)
- No requirement for concurrent antibiotics or antifungal agents for the
prevention of opportunistic infections
- A CD4 count above 250 cells/mcL, and an undetectable HIV viral load on standard
polymerase chain reaction (PCR)-based tests
- No other planned concurrent investigational agents or other tumor directed therapy
(chemotherapy, radiation) while on study
- No systemic daily treatment with either corticosteroids (> 10 mg daily prednisone
equivalents) or other immunosuppressive medications within 7 days of registration
- No known history of severe allergic anaphylactic reactions to chimeric, human or
humanized antibodies, or fusion proteins
- No known hypersensitivity to Chinese hamster ovary (CHO) cell products or any
component of the atezolizumab formulation
- No known allergy to 5-fluorouracil, oxaliplatin, or leucovorin
Exclusion Criteria:
- Patients with testing that did not show dMMR (loss of MMR protein) are not eligible
to participate; patients whose tumors show MSI-H by PCR-based assay are not eligible
to participate unless they also have MMR testing by IHC and are found to have dMMR
(i.e. loss of one or more MMR proteins)
- Excluded if known active pulmonary disease with hypoxia defined as:
- Oxygen saturation < 85% on room air, or
- Oxygen saturation < 88% despite supplemental oxygen