Interventional, prospective, randomized (1:1), controlled, open label, multicenter phase IIb study in patients with advanced metastatic colorectal cancer. The scope of the trial is to evaluate overall survival of either regimen (TAS102 +/- Ramucirumab) and evaluate safety and tolerability.
Name: Ramucirumab
Description: 8 mg/kg iv over 60 min on d1+15, q4wType: DrugArm A (ramucirumab + TAS102)
Name: TAS 102
Description: 35mg/m2 p.o. twice daily (BID) d1-5 and d8-12, q4wType: DrugArm A (ramucirumab + TAS102) Arm B (TAS102 only)
Description: Overall survival according to Kaplan-Meier
Measure: Overall survival Time: Up to 3 yearsDescription: ORR defined as the proportion of patients with complete or partial remission according to RECIST 1.1
Measure: Overall response rate (ORR) Time: Up to 3 yearsDescription: DCR defined as the proportion of patients with complete or partial remission and stable disease according to RECIST 1.1
Measure: Disease control rate (DCR) Time: Up to 3 yearsDescription: PFS, defined as the time from enrollment/randomization to the first occurrence of progression, as determined by the investigator using CT criteria, or death from any cause
Measure: Progression-free survival (PFS) Time: Up to 3 yearsDescription: OS rate at 6 and 12 months, defined as patients who are alive after at 6 and 12 months, respectively
Measure: Overall survival (OS) at different time points Time: 6 months and 1 yearDescription: Efficacy (ORR) in patients who develop neutropenia grade ≥2 (ANC ≤1500/μl) in cycle 1
Measure: Efficacy (ORR) Time: Up to 3 yearsDescription: Efficacy (PFS) in patients who develop neutropenia grade ≥2 (ANC ≤1500/μl) in cycle 1
Measure: Efficacy (PFS) Time: Up to 3 yearsDescription: Efficacy (OS) in patients who develop neutropenia grade ≥2 (ANC ≤1500/μl) in cycle 1
Measure: Efficacy (OS) Time: Up to 3 yearsDescription: Quality of life (QoL) as measured by EORTC-QLQ-C30 at d1 of each cycle and on EOT (end of treatment).
Measure: Quality of life I (QoL) Time: Up to 1 yearDescription: Quality of life (QoL) as measured by EQ-5D-5L at d1 of each cycle and on EOT.
Measure: Quality of life II (QoL) Time: Up to 1 yearDescription: ORR according to gene expression, mutational profiles and plasma biomarkers
Measure: Explorative: Overall response rate (ORR) Time: Up to 3 yearsDescription: OS according to gene expression, mutational profiles and plasma biomarkers
Measure: Explorative: Overall survival (OS) Time: Up to 3 yearsDescription: PFS according to gene expression, mutational profiles and plasma biomarkers
Measure: Explorative: Progression-free survival (PFS) Time: Up to 3 yearsAllocation: Randomized
Parallel Assignment
There is one SNP
Intolerance is defined as a permanent discontinuation of the respective treatment resulting from toxicity 2. Signed informed consent before start of specific protocol procedure 3. Histologically or cytologically documented diagnosis of adenocarcinoma of the colon or rectum 4. Presence of at least one measurable site of disease following RECIST 1.1 criteria 5. ECOG (Eastern Cooperative Oncology Group) performance 0-1 6. Known RAS and BRAF V600E mutational status 7. Life expectancy of at least 3 months 8. Adequate hematological, hepatic and renal function parameters: 1. Leukocytes ≥3000/mm³, platelets ≥100,000/mm³, neutrophil count (ANC) ≥1500/μL, hemoglobin ≥9 g/dL (5.58 mmol/L) 2. Adequate coagulation function as defined by International Normalized Ratio (INR) ≤1.5, and a partial thromboplastin time (PTT) ≤5 seconds above the ULN (upper limit of normal) (unless receiving anticoagulation therapy). --- V600E ---
Patients will be stratified by the duration of previous anti-angiogenic therapy ≥ or <12 months in total, BRAF V600E mutation status (mutation vs. wildtype), RAS mutation status (mutation vs. wildtype), and randomized 1:1 to receive either ramucirumab/TAS102 (arm A) or TAS102 (arm B). --- V600E ---