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

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