Maintenance Therapy With 5-FU/FA Plus Panitumumab vs. 5-FU/FA Alone After Prior Induction and Re-induction After Progress for 1st-line Treatment of Metastatic Colorectal Cancer (PanaMa)
Metastatic Colorectal Cancer
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring metastatic colorectal cancer, maintenance therapy, Panitumumab, Vectibix®
Eligibility Criteria
Inclusion Criteria:
- Signed written informed consent
- Male or female ≥ 18 years of age
- Histologically proven metastatic colorectal cancer
- Molecular testing showing RAS wild-type in colorectal carcinoma cells
- Life expectancy > 12 weeks
- At least one measurable lesion according to RECIST 1.1
- Adequate bone marrow, liver, kidney, organ and metabolic function
Bone marrow function:
- leukocyte count ≥ 3.0 × 109/L
- ANC ≥ 1.5 × 109/L
- platelet count ≥ 100 × 109/L
- hemoglobin ≥ 9 g/dL or 5.59 mmol/L (may be transfused or treated with erythropoietin to maintain/ exceed this level)
Hepatic function:
- Total bilirubin ≤ 1.5 × UNL
- ALT and AST ≤ 2.5 × UNL (or ≤ 5 × UNL in presence of liver metastases)
- AP ≤ 5 × UNL
Renal function:
- Creatinine clearance ≥ 50 mL/min according to Cockcroft-Gault formula or serum creatinine ≤ 1.5 × UNL
Metabolic function:
- Magnesium ≥ lower limit of normal
- Calcium ≥ lower limit of normal
- ECOG performance status 0 - 1
- Women of child-bearing potential must have a negative pregnancy test
Exclusion Criteria:
- Previous treatment for colorectal cancer in the metastatic setting
- Previous EGFR-targeting therapy < 6 months after end of adjuvant therapy
- Known brain metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids
- Chronic inflammatory bowel disease
- Peripheral neuropathy ≥ NCI-CTCAE V 4.03 grade 2
- Other previous malignancies with the exception of a history of previous curatively treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix or other curatively treated malignant disease without recurrence after at least 5 years of follow-up
- Significant disease that, in the investigator's opinion, would exclude the patient from the study
History of cardiac disease; defined as:
- Congestive heart failure > New York Heart Association (NYHA) class 2
- Active coronary artery disease (myocardial infarction more than 6 months prior to start of study treatment is allowed)
- Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted)
- Uncontrolled hypertension (defined as blood pressure ≥ 160 mmHg systolic and/or ≥ 90 mmHg diastolic on medication)
- Patients with interstitial lung disease, e.g., pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
- Known HIV, hepatitis B or C infection
- Known hypersensitivity reaction to any of the study components
- Radiotherapy, major surgery or any investigational drug 30 days before registration
- Pregnancy or lactation or planning to be pregnant during treatment and within 6 months after the end of treatment
- Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for at least an additional 6 months after the end of treatment
- Known alcohol or drug abuse
- Any condition that is unstable or could jeopardize the safety of the patient and his compliance in the study
Sites / Locations
- St.-Antonius-Hospital Eschweiler
- Zentrum für Tumorbiologie und Integrative Medizin, Klinikum Wilhelmshaven
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Maintenance Chemotherapy + Panitumumab
Maintenance Chemotherapy w/o Panitumumab
Maintenance therapy: Panitumumab 6 mg/kg prior to administration of chemotherapy Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15 Re-induction upon progression: Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy. mFOLFOX6: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
Maintenance therapy: Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15 Re-induction upon progression: Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy. mFOLFOX6 chemotherapy: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15