Patient case: 49-year-old male with colorectal cancer; genetic feature: NRAS

Clinical trial: 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

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: 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

Relevance to patient case: not relevant