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

Conditions: Metastatic Colorectal Cancer

Summary: this is a phase ii, randomized, multi-center, open-label, parallel-group study to evaluate the progression-free survival during maintenance therapy. eligible patients will be treated within a 12-week induction therapy. those patients achieving cr/pr or sd at 12 weeks and qualifying for maintenance treatment and re-induction treatment with all potential drug components, will be randomized in a ratio of 1:1 to receive chemotherapy plus panitumumab or chemotherapy alone during maintenance. in case of progression, re-induction treatment will be started.


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

Keywords: metastatic colorectal cancer maintenance therapy panitumumab vectibix®