Nintedanib and Capecitabine in Treating Patients With Refractory Metastatic Colorectal Cancer

Inclusion Criteria:

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) AND creatinine clearance (CrCl) > 50 mL/min by Cockcroft-Gault equation
Males = (140 -age (yrs) (body weight (kg)/(72) (serum creatinine) (mg/dL)
Females = 0.85 * (140-age (yrs) (body weight (kg)/(72)(serum creatinine (mg/dL)
Bilirubin < ULN
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 1.5 ULN if without liver metastases
AST/ALT =< 2.5 x ULN if with liver metastases
Coagulation parameters: international normalized ratio (INR) =< 2, prothrombin time (PT) and partial thromboplastin time (PTT) < 1.5 X institutional ULN
Have measurable disease per RECIST 1.1 criteria
Histologically or cytologically proven adenocarcinoma of the colon or rectum
Prior progression following a fluoropyrimidine-based therapy and progression following or intolerance to irinotecan and oxaliplatin, as well as anti-epidermal growth factor receptor (EGFR) therapy (e.g., panitumumab or cetuximab) for rat sarcoma viral oncogene homolog (RAS) wild-type patients
Ability to swallow and retain oral medication
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 and for three months following completion of therapy; 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 or legal representative 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 nintedanib
Prior treatment with regorafenib
Major injuries or surgery within the 4 weeks prior to initiation of therapy with incomplete wound healing or planned surgery during the on-study treatment period
Uncontrolled hypertension: systolic blood pressure >= 160, diastolic blood pressure >= 90
Urine protein/creatinine ratio >= 1.0
History of clinically significant hemorrhagic or thrombotic event within the past 6 months, not including uncomplicated catheter-associated venous thrombosis; patients on anti-coagulation are not permitted to be on any oral formulations (warfarin, rivaroxaban, dabigatran, etc.) due to concern for drug-drug interaction
Unstable angina, symptomatic congestive heart failure or cardiac arrhythmia requiring anti-arrhythmic therapy (beta-blockers, calcium channel blockers and digoxin are allowed)
History of cerebrovascular or myocardial ischemia within 6 months of initiation
Known inherited predisposition to bleeding or thrombosis
Known active or chronic hepatitis B or C or human immunodeficiency virus (HIV)
Untreated brain metastases

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

In-situ cervical carcinoma
Superficial bladder cancer
Non-melanoma skin cancer
Stage I breast cancer
Low grade (Gleason =< 6) localized prostate cancer
Any additional malignancy which has been in clinical remission for at least 1 year
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
Received an investigational agent within 4 weeks prior to enrollment
PHASE I: History of intolerance to capecitabine at doses =< 1000 mg/m^2 BID, as defined by documented >= grade 3 hand-foot syndrome, documented severe diarrhea requiring hospitalization, or other documented severe adverse events (AEs) attributable to capecitabine
PHASE II: History of intolerance to capecitabine at doses below 1000 mg/m^2 BID, as defined by documented >= grade 3 hand-foot syndrome; documented severe diarrhea requiring hospitalization; or other documented severe AEs attributable to capecitabine