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

• Status: Recruiting
• Trial end date: 2022-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to compare progression free survival rates of metastasized colorectal cancer patients refractory or intolerant to systemic therapy with fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy and anti-EGFR therapy (for tumours with wild-type KRAS)); randomized for treatment with TAS-102 (standard-arm) or High Dose Intermittent Sunitinib (700 mg once every 2 weeks). The investigators hypothesis is that treatment with the experimental arm (sunitinib) will provide an improvement in progression free in this patient group.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: VU University Medical Center
• Treatments: Sunitinib

Criteria

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.