| Eligibility |
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed colorectal cancer with
liver metastases deemed resectable by a general or liver surgeon (resectability may
involve the use of ablative techniques to some but not all liver metastases); those
patients with known disease outside of the liver are not eligible (except for patients
with primary lesions in place that are planned for resection or nonspecific lung
metastases < 1 cm)
- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >=
10 mm with spiral computed tomography (CT) scan
- All lines of prior therapy accepted; subjects with prior hepatic or extra-hepatic
resections of metastatic disease will be included
- Life expectancy of greater than 6 months
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin < 1.5 X institutional normal limits (subjects with known Gilbert
syndrome are eligible with total bilirubin < 3.0 mg/dL)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) =<
3 X institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance >= 60
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Known or ordered molecular testing for MSI, BRAF, and KRAS status
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female pre-menopausal patients; women will be considered post-menopausal if they have
been amenorrheic for 12 months without an alternative medical cause; the following
age-specific requirements apply:
- Women < 50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and if they have luteinizing hormone and follicle-stimulating hormone
levels in the post-menopausal range for the institution or underwent surgical
sterilization (bilateral oophorectomy or hysterectomy)
- Women >= 50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatments, had radiation-induced menopause with last menses > 1 year ago, had
chemotherapy-induced menopause with last menses > 1 year ago, or underwent
surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
hysterectomy)
- Ability to understand and the willingness to sign a written informed consent document
- Weight > 30 kg (required for flat dose-based administration of study agents)
Exclusion Criteria:
- Prior chemotherapy < 2 weeks prior to study drug treatment and treatment related
adverse events that have not recovered to baseline or grade 1 (alopecia excluded);
prior radiation therapy < 4 weeks prior to study drug treatment
- Patients may not be receiving any other investigational agents
- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome,
or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
arthritis, hypophysitis, uveitis, etc.]); the following are exceptions to this
criterion: a) patients with vitiligo or alopecia; b) patients with hypothyroidism
(e.g., following Hashimoto syndrome) stable on hormone replacement; c) any chronic
skin condition that does not require systemic therapy; d) patients without active
disease in the last 5 years may be included but only after consultation with the study
physician; d) patients with celiac disease controlled by diet alone
- Subjects with a condition requiring systemic treatment with either corticosteroids (>
10 mg daily prednisone equivalents) or other immunosuppressive medications within 14
days of study drug administration; inhaled or topical steroids and adrenal replacement
doses > 10 mg daily prednisone equivalents are permitted in the absence of active
autoimmune disease
- Prior exposure to T cell checkpoint inhibitor therapies, including durvalumab and
tremelimumab
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, interstitial lung disease, symptomatic congestive heart failure, unstable
angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that
would limit compliance with study requirements
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients
- History of active primary immunodeficiency
- Women who are pregnant, which includes women with a positive pregnancy test at
enrollment or prior to the administration of study medication, or breastfeeding are
not allowed on study
- Receipt of a live vaccine within 30 days of study entry
- Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria
for Adverse Events (CTCAE) grade >= 2 from previous anticancer therapy with the
exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
criteria: a) patients with grade >= 2 neuropathy will be evaluated on a case-by-case
basis after consultation with the study physician; b) patients with irreversible
toxicity not reasonably expected to be exacerbated by treatment with durvalumab or
tremelimumab may be included only after consultation with the study physician
- Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment,
concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone
replacement therapy) is acceptable
- Major surgical procedure within 28 days prior to the first dose of IP; Note: local
surgery of isolated lesions for palliative intent is acceptable
- History of allogenic organ transplantation
- Known active infection including tuberculosis (clinical evaluation that includes
clinical history, physical examination and radiographic findings, and tuberculosis
[TB] testing in line with local practice), hepatitis B (known positive hepatitis B
virus [HBV] surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency
virus (positive HIV 1/2 antibodies); patients with a past or resolved HBV infection
(defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg)
are eligible; patients positive for hepatitis C (hepatitis C virus [HCV]) antibody are
eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
- Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab monotherapy or 180 days after
the last dose of durvalumab + tremelimumab combination therapy
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