Aflibercept and 5-FU vs. FOLFOX as 1st Line Treatment for Elderly or Frail Elderly Patients With Met. Colorectal Cancer (ELDERLY)
Colorectal Cancer
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring colorectal cancer, 5-FU, Aflibercept, Oxaliplatin
Eligibility Criteria
Inclusion Criteria:
- To enter this trial the oncologist has to confirm, that the patient was in his or her opinion not a candidate for standard full-dose combination therapy. Moreover, the oncologist has to state the reason for entering the trial (Advanced age alone versus both age and frailty). As an operational definition for frailty the G8 screening tool will be used upon inclusion of the patient in a standardized manner. Briefly, G8 is an established screening tool that includes seven items from the Mini Nutritional Assessment (MNA) and an age-related item (<80, 80 to 85, or 85 years). The total score can range from 0 to 17. The result on the G8 is considered abnormal if the score is ≤14, indicating a geriatric risk profile.
- Patients have to have histologically confirmed mCRC with unidimensionally measurable inoperable advanced or metastatic disease
- ECOG performance status of 2 or better.
- Life expectancy of 3 months or longer at enrolment
- Patients >70 years with no upper age limit
- Previous adjuvant chemotherapy is allowed if completed more than 6 months before randomisation
- Previous rectal (chemo)radiotherapy is allowed if completed more than 6 months before randomisation
Hematological status:
- Neutrophils (ANC) ≥ 1.5 x 109/L
- Platelets ≥ 100 x 109/L
- Hemoglobin ≥ 9 g/dL
Adequate renal function:
• Serum creatinine level ≤ 1.5 x upper limit normal (ULN)
Adequate liver function:
- Serum bilirubin ≤ 1.5 x upper limit normal (ULN)
- Alkaline phosphatase ≤ 2.5 x ULN (unless liver metastases are present, then < 5 x ULN in that case)
- AST and ALT < 3 x ULN (unless liver metastases are present then < 5 x ULN in that case)
- Proteinuria < 2+ (dipstick urinalysis) or ≤ 1 g/24hour
- Signed and dated informed consent, and willing and able to comply with protocol requirements
- Regular follow-up feasible
- Male patients with a partner of childbearing potential must agree to use effective contraception (Pearl Index < 1) during the course of the trial and at least 3 months after last administration of the study drug.
Exclusion Criteria:
- Prior systemic chemotherapy for mCRC
Other concomitant or previous malignancy, except:
- Adequately treated in-situ carcinoma of the uterine cervix
- Basal or squamous cell carcinoma of the skin
- Cancer in complete remission for > 5 years
- Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 Days
- History or evidence upon physical examination of CNS metastasis unless adequately treated (irradiation and no seizure with appropriate treatment)
- Uncontrolled hypercalcemia
- Pre-existing peripheral neuropathy (NCI grade ≥2)
- Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
- Treatment with any other investigational medicinal product within 28 days prior to study entry.
Significant cardiovascular disease:
- Cardiovascular accident or myocardial infarction or unstable angina ≤6 months before start of study treatment
- Severe cardiac arrhythmia
- New York Heart Association grade ≥2 congestive heart failure
- Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy.
- History of stroke or transient ischemic attack ≤6 months before start of study treatment
- Coronary/peripheral artery bypass graft ≤6 months before start of study treatment.
- Deep vein thrombosis or thromboembolic events ≤1 month before start of study treatment
- Patients with known allergy to any excipient to study drugs,
- Any of the following within 3 months prior to randomization: Grade 3-4 gastrointestinal bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event.
- Bowel obstruction.
- Treatment with CYP3A4 inducers unless discontinued > 7 days prior to randomization
- Known dihydropyrimidine dehydrogenase (DPD) deficiency
- Involvement in the planning and/or conduct of the study (applies to both Sanofi staff and/or staff of sponsor and study site)
- Patient who might be dependent on the sponsor, site or the investigator
- Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.
- Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].
Sites / Locations
- Phase Drei
- HELIOS Klinikum Bad Saarow
- Klinikum Bayreuth
- MVZ Seestrasse
- Klinikum Bremen Nord
- Kliniken Essen-Mitte
- Agaplesion Markus Krankenhaus
- Krankenhaus Nordwest GmbH
- Klinikum Garmisch-Partenkirchen GmbH
- Nationales Centrum für Tumorerkrankungen (NCT)
- Städtisches Klinikum Karlsruhe
- DRK-Kliniken Nordhessen gGmbH
- Ortenau Klinikum Lahr
- Onkologisches Zentrum
- Klinikum Ludwigshafen
- Klinikum Magdeburg gGmbH
- Tagestherapiezentrum am ITM Universitätsmedizin Mannheim
- Kliniken Ostalb
- Klinikum der Universität München-Großhadern
- Kliniken des Landkreises Neumarkt in der Oberpfalz
- Studienzentrum Onkologie Ravensburg
- Clinical Research Stolberg GmbH
- Klinikum Mutterhaus Trier
- Universitätsklinikum Tübingen
- Klinikum Wilhelmshaven
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Arm A (mFOLFOX7)
Arm B (Aflibercept + mLV5FU2)
Patients in the 5-FU / oxaliplatin arm receive modified (m) FOLFOX 7: Folinic acid 350 mg/m² and oxaliplatin 68 mg/m² by concurrent 2-h intravenous infusion, 5-fluorouracil 1920 mg/m² 46-h intravenous infusion every 2 weeks (qd15). This regimen represents the 80% dosage reduced mFOLFOX 7. The 80% dose reduction was shown to be a tolerable regimen in frail elderly patients in the FOCUS 2 study.
Patients in the 5-FU / aflibercept arm receive aflibercept 4mg/kg as 1-h infusion followed by folinic acid 350 mg/m² by 2-h intravenous infusion, 5-fluorouracil 1920 mg/m² 46-h intravenous infusion (mLV5FU2) every 2 weeks (qd15). The decision to use reduced doses of 5-FU and folinic acid was made to have comparable doses to the reduced FOLFOX 7.