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

Randomized Phase II Study for Evaluation of Efficacy and Safety of Maintenance Treatment With 5-FU/FA Plus Panitumumab vs. 5-FU/FA Alone After Prior Induction Treatment With mFOLFOX6 Plus Panitumumab and Re-induction With mFOLFOX6 Plus Panitumumab in Case of Progression for First-line Treatment of Patients With 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.

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