Pulsatile High-dose Sunitinib Versus TAS-102 in Patients With Metastatic Colorectal Carcinoma (mCRC)

Inclusion Criteria:

* Signed (by the patient or legally acceptable representative) and dated Informed Consent Form (ICF).
* Histological or cytological confirmed, documentation of incurable locally advanced or metastatic, colorectal adenocarcinoma, not amenable for potentially curative treatment (i.e. inoperable).
* Indication for treatment with TAS-102; progressive on (or intolerant to) therapy including fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy and anti-EGFR therapy (for tumours with wild-type KRAS)).
* Evaluable disease by RECIST version 1.1 criteria (see appendix III).
* Age ≥ 18 years.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 3.
* Normal 12-lead ECG (clinically insignificant abnormalities permitted).
* No signs of clinical thyroid abnormalities (suppletion or blocking drugs permitted).
* Adequate bone marrow function
* Adequate liver function
* Albumin higher than 25 g per L
* Serum creatinine ≤1.5 x ULN
* Pregnant or breast-feeding subjects: Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. For fertile men or women of childbearing potential: documented willingness to use a highly effective means of contraception (e.g., hormonal methods \[implants, injectables, or combined oral contraceptives\], intrauterine devices, sexual abstinence, or vasectomized or surgically sterilized partner). Contraception is necessary for at least 6 months after receiving the study medication.

Exclusion Criteria:

* Previous treatment with sunitinib and/or TAS-102 for mCRC.
* Evidence of significant uncontrolled concomitant disease, such as cardiovascular disease (including stroke, New York Heart Association Class III or IV cardiac disease or myocardial infarction within 6 months prior to screening, unstable arrhythmia, clinically significant valvular heart disease and unstable angina); pulmonary disease (including obstructive pulmonary disease \> GOLD 2 and inadequately treated symptomatic bronchospasm), and uncontrolled central nervous system, renal, hepatic, endocrine, or gastrointestinal disorders; or a serious non-healing wound or fracture.
* Extensive prior radiotherapy in the rectum, pelvis or in more than 3 vertebrae in the spine (less than 3 vertebrae are considered a small radiation field and eligibility will be decided on an individual basis from the PI).
* Poorly controlled hypertension despite adequate blood pressure medication. Blood pressure must be ≤160/95 mmHg at the time of screening on a stable antihypertensive regimen. Blood pressure must be stable on at least 2 separate measurements.
* Instable seizure disorders requiring anticonvulsant therapy.
* Major surgery, other than diagnostic surgery, within 4 weeks prior to day 1, without complete recovery.
* Uncontrolled bleeding disorders, and/or active bleeding.
* Known active bacterial, viral, fungal, mycobacterial, or other infection. (including HIV and atypical mycobacterial disease, but excluding fungal infection of the nail beds.)
* Known hypersensitivity to sunitinib, TAS-102, or to its excipients.
* Presence of any significant psychiatric disorder(s) that would interfere with the patient's compliance.
* Chemotherapy, radiotherapy, or other anti-cancer therapy within the previous 4 weeks; no nitrosoureas or mitomycin C within the previous 6 weeks; no investigational agents within the previous 4 weeks.
* Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
* Untreated or active central nervous system (CNS) metastases.
* Predisposing colonic or small bowel disorders in which the symptoms are uncontrolled as indicated by baseline of \> 3 loose stools daily despite medication.
* Unresolved bowel obstruction
* Any evidence of a disease or condition that might affect compliance with the protocol or interpretation of the study results or render the patient at high risk from treatment complications.