Advanced colorectal tumors
Conditions
Interventions
Trade Name: Sutent
Product Name: sunitinib
Product Code: L01XE04
Pharmaceutical Form: Tablet
Sponsors
VU University Medical Center, Department of Medical
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible for this trial, patients will need to meet all of the following inclusion criteria. Screening must be performed no more than 14 days prior to the first study drug dose. 1: Signed (by the patient or legally acceptable representative) and dated Informed Consent Form (ICF). 2: Histological or cytological confirmed, documentation of incurable locally advanced or metastatic, colorectal adenocarcinoma, not amenable for potentially curative treatment (i.e. inoperable). 3: 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)). 4: Evaluable disease by RECIST version 1.1 criteria (see appendix III). 6: Age = 18 years. 7: Eastern Cooperative Oncology Group (ECOG) Performance Status of 5.6 mmol/l, absolute neutrophil count (ANC) >1,5 x 10*9/l, Platelet count ? 100 x 10*9/l, 11: Adequate liver function; total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: The following criteria exclude the patient from enrollment in this trial 1: Previous treatment with sunitinib and/or TAS-102 for mCRC. 2: 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. 3: 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). 4: 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. 5: Instable seizure disorders requiring anticonvulsant therapy. 6: Major surgery, other than diagnostic surgery, within 4 weeks prior to day 1, without complete recovery. 7: Uncontrolled bleeding disorders, and/or active bleeding. 8: Known active bacterial, viral, fungal, mycobacterial, or other infection. (including HIV and atypical mycobacterial disease, but excluding fungal infection of the nail beds.) 9: Known hypersensitivity to sunitinib, TAS-102, or to its excipients. 10: Presence of any significant psychiatric disorder(s) that would interfere with the patient’s compliance. 11: 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. 12: Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis. 13: Untreated or active central nervous system (CNS) metastases. 14: Predisposing colonic or small bowel disorders in which the symptoms are uncontrolled as indicated by baseline of > 3 loose stools daily despite medication. 15: Unresolved bowel obstruction 16: 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to improve progression free survival (PFS), of patients with metastatic colorectal carcinoma (mCRC) treated with high-dose sunitinib once every 2 weeks to 5 months, compared to the reported 2 months for TAS-102 monotherapy;Secondary Objective: Secondary objectives are: 1: Overall Survival (OS), counting from the date of study inclusion to the date of death of the patient (from any cause) or to the last day of follow-up. 2: To determine quality of life (QoL) of patients in the study. 3: To determine safety and tolerability of the two drugs. 4. Liquid biopsies for circulating blood biomarker analysis including microRNA and platelets containing tumor-derived RNA. 5. A cost effectiveness (utility) analysis will be performed from a health care perspective. 6. Phosphoproteomics profiling on tumor biopsy. ;Primary end point(s): The primary objective of this study is to improve PFS of patients with stage IV colorectal carcinoma, who progressed on (or are intolerant to) 5-FU, oxaliplatin, irinotecan, anti-VEGF (and/or anti-EGFR) containing therapy, treated with high-dose sunitinib (once every 2 weeks) to 5 months, compared to 2 months for patients treated with TAS-102 monotherapy. Progression free survival is defined as the time from randomization to the date of the first documented tumor progression as determined by the investigator using RECIST 1.1 criteria or death due to any cause. PFS between patients included in the two different study arms will be compared.;Timepoint(s) of evaluation of this end point: After 9-10 weeks of treatment by CT-scan (RECIST 1.1) and every 2 weeks by physical exam en laboratory exam. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary objectives are: 1: Overall Survival (OS), counting from the date of study inclusion (and randomization) to the date of death of the patient (from any cause) or to the last day of follow-up. 2: To determine quality of life (QoL) of patients in the study. The difference in quality of life between two treatment arms will be assessed. Patients will complete the European Organisation for Research and Treatment of Cancer Quality of Life questionnaires (EORTC QoL) to evaluate this objective. A total of 2 questionnaires will be included; EORTC QlQ-C30 Version 3.0 to assess QoL of cancer patients in general and EORTC-QLQ-CR29 to asses QoL of CRC cancer patients. 3: To determine safety and tolerability of the two drugs. In this study two therapeutic drugs are compared in an attempt to improve survival of patients with CRC. TAS-102 had been previously safely used in patients with mCRC. Sunitinib is already registered for various cancer types with acceptable toxicity, but not at this dosing regimen and for mCRC. Safety and tolerability will be studied by analysis of adverse events, physical examinations, vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, and laboratory-abnormality assessments (complete blood count with differential count, serum electrolyte measurements, and electro cardiogram). Severity of adverse events will be rated by investigators by use of the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.27. CTCAE (2006) 4. Liquid biopsies for circulating blood biomarker analysis including microRNA and platelets containing tumor-derived RNA. Evaluation of potentially predictive circulating biomarkers could help in identifying patients, rather easily by venepuncture, who will not benefit from treatment and thereby may provide a potential selection tool to avoid unnecessary treatment and its associated toxicity. The potential value of blood markers for molecular diagnostics | — |
Countries
Netherlands
Contacts
Public ContactDepartment of Medical Oncology
VU University Medical Center
Outcome results
None listed