| Eligibility |
Inclusion Criteria:
1. Written informed consent in accordance with federal, local, and institutional
guidelines
2. Patients must have histologically/pathologically confirmed colorectal adenocarcinoma
with measurable disease by RECIST 1.1 criteria
3. Patients must have had no prior chemotherapy for metastatic disease with
fluoropyrimidine based chemotherapy with oxaliplatin or irinotecan
4. Patients with prior adjuvant chemotherapy are allowed, as long as a minimum of 6
months have passed between the completion of adjuvant therapy and the start of the
study medication
5. Age >18 years
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
7. Radiographic evidence of metastatic disease
8. At the time of study entry:
absolute neutrophil count must be = 1000/mm3, hemoglobin = 9 gm/dL, and platelet count
= 100,000/mm3 There must be evidence of adequate hepatic and renal function. Bilirubin
must be = 1.5 x upper limit of normal (ULN) for the lab unless the patient has a
chronic grade 1 bilirubin elevation due to Gilbert's disease or similar syndrome due
to slow conjugation of bilirubin Alkaline phosphatase must be = 3 x ULN for the lab
AST and ALT must be = 5 x ULN for the lab Serum creatinine = 1.5 x ULN for the lab
Note: For patients with liver metastases, non-fasting bilirubin 1.5 x ULN to 3 x ULN
of the institution's normal range are acceptable.
9. Both male and female patients with childbearing potential must agree to use
adequatecontraception throughout the study and for 9 months after last dose of
mFOLFIRINOX, bevacizumab or CPI-613 (devimistat)
10. Patients without liver metastasis are eligible if they have ALT and AST = 3.0 x ULN
Exclusion Criteria:
1. Diagnosis of anal or small bowel carcinoma
2. Colorectal cancer other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid
3. Patients with tumors that are MSI-high/dMMR
4. Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days ofreceiving study therapy
5. Active infection or chronic infection requiring systemic therapy
6. Known history of human immunodeficiency virus (HIV) or acquired
immunodeficiencyrelated (AIDS) illnesses with CD4 count < 250 cells/mm3
7. Any of the following cardiac conditions:
Documented NYHA Class III or IV congestive heart failure, Myocardial infarction within
6 months prior to study entry, Unstable angina within 6 months prior to study entry,
Symptomatic arrhythmia
8. Other malignancies unless the patient is considered to be disease-free and has
completed therapy for the malignancy = 12 months prior to study entry.
Patients with the following cancers are eligible if diagnosed and treated within the
past 12 months: carcinoma in situ of the cervix, and basal cell and squamous cell
carcinoma of the skin
9. Psychiatric or addictive disorders or other conditions that in the opinion of the
investigator would preclude the patient from meeting the study requirements or
interfere with interpretation of study results
10. Any other chronic or clinically significant medical condition that in the opinion of
investigator would jeopardize the safety or rights of the volunteer. Including, but
not limited to: diabetes mellitus type I, chronic hepatitis; OR clinically significant
forms of drug oralcohol abuse, asthma, autoimmune disease, psychiatric disorders,
heart disease, or cancer. Patients must have neuropathy grade 1 or less
11. Pregnancy or lactation at the time of study entry
12. Use of any investigational agent within 4 weeks prior to the first dose study therapy
13. Patients with the following conditions:
Uncontrolled hypertension (defined as systolic blood pressure = 150 mm Hg and
diastolic blood pressure = 100 mm Hg) Bleeding diatheses or hemorrhage within 6 months
prior of study enrollment Gastrointestinal perforation or fistulas History of
thromboembolic events Reversible Posterior Leukoencephalopathy Syndrome (RPLS),
Proteinuria > 1gr/24 hours
14. Patients with current serious, non-healing wound, ulcer and baseline peripheral
neuropathy of grade 2 or greater, hypersensitivity reaction to 5-FU, oxaliplatin or
other platinum-based drugs, or irinotecan if it was previously administered in the
adjuvant setting
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