A Phase II Study of TAS-102, Irinotecan and Bevacizumab in Pretreated Metastatic Colorectal Cancer.

Inclusion Criteria

- Advanced colorectal cancer (metastatic or unresectable): Histologically or cytological

proven adenocarcinoma of the colon or rectum which is metastatic or otherwise

incurable

- Prior treatment with a fluoropyrimidine (5-fluorouracil [5-FU] or capecitabine) and

oxaliplatin in the metastatic/unresectable setting OR, recurrence within 12 months of

adjuvant therapy with a regimen that included oxaliplatin

- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

- Hemoglobin >= 9 g/dL

- Absolute neutrophil count >= 1500/mm^3

- Platelet count >= 100,000/mm^3

- Creatinine < 1.5 upper limit of normal (ULN) or if >= 1.5 x ULN creatinine clearance

(CRCL) >= 30 mL/min (by Cockcroft-Gault)

- Bilirubin < 1.5 x ULN

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN or =< 5 x

ULN if with hepatic metastases

- Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

criteria present

- Participants of child-bearing potential must agree to use adequate contraceptive

methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study

entry. Should a woman become pregnant or suspect she is pregnant while she or her

partner is participating in this study, she should inform her treating physician

immediately

- Participant must understand the investigational nature of this study and sign an

Independent Ethics Committee/Institutional Review Board approved written informed

consent form prior to receiving any study related procedure

Exclusion Criteria

- Prior treatment with TAS-102 or irinotecan

- Anti-cancer therapy within 2 weeks of the planned first dose of study medication

- Unresolved toxicities from prior therapy of > grade 1, excluding alopecia or similar

toxicities which are not deemed to be clinically significant or put the participant at

greater risk. Grade 2 neuropathy is permitted

- Major surgery within 4 weeks of anticipated start of therapy

- Uncontrolled hypertension: systolic blood pressure >= 150, diastolic blood pressure >=

100

- Unstable angina, symptomatic congestive heart failure or cardiac arrhythmia requiring

anti-arrhythmic therapy (beta-blockers, calcium channel blockers and digoxin are

allowed)

- Arterial or venous thrombotic or embolic events within 3 months of study initiation,

unless well controlled on stable anti-coagulation for >= 2 weeks. This excludes

uncomplicated catheter associated venous thrombosis

- History of cerebrovascular or myocardial ischemia within 6 months of initiation

- National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)

version (v) 5.0 grade 3 or greater hemorrhage within the past 4 weeks

- Proteinuria >= 2+, unless 24 hour urine collection demonstrates =< 1 g of protein OR

spot protein: creatinine demonstrates a ratio of =< 1

- Untreated brain metastases

- History of abnormal glucuronidation of bilirubin (Gilbert's syndrome)

- History of second primary malignancy within 3 years prior to enrollment, excluding

in-situ cervical carcinoma, non-melanoma skin cancer or malignancy of equivalent risk

which is highly unlikely to require systemic treatment in the next 2 years

- Have known active infection which would heighten the risk of complications

- Pregnant or nursing female participants

- Unwilling or unable to follow protocol requirements

- Any condition which in the investigator's opinion deems the participant an unsuitable

candidate to receive study drug