MONARCC: This phase II trial is trying to determine whether it is better to give a targeted therapy (Panitumumab) alone or in combination with standard chemotherapy (5-FU) as a primary treatment for advanced colorectal cancerA randomised phase II study of Panitumumab monotherapy and panitumumab plus 5 fluorouracil as first line therapy for RAS and BRAF wild type metastatic colorectal cancer

Inclusion

1. Adults aged 70years and over.
2. Histologically or cytologically confirmed, previously untreated, metastatic colorectal cancer.
3. Suitable for panitumumab or panitumumab plus infusional 5FU, as deemed by the investigator.
4. Measurable metastatic disease (by RECIST 1.1)
5. RAS (KRAS exons 2,3 and 4; NRAS exons 2 and 3) wild type as assessed by the investigator’s choice of testing laboratory.
6. BRAF wild type as assessed by the investigator’s choice of testing laboratory. Patients with BRAF V600E mutations are not eligible. Patient with non-V600E BRAF mutations (if tested for) are eligible.
7. No prior chemotherapy except for adjuvant chemotherapy given in association with (i) complete resection of primary colon or rectal cancer provided there is no clinical, radiological or biochemical evidence of relapse for at least 6 months after completion of adjuvant treatment and/or (ii) complete resection of limited colorectal metastases to liver and/or lung provided there is no clinical, radiological or biochemical evidence of relapse for at least 6 months after completion of adjuvant treatment
8. Prior palliative radiotherapy is allowed, provided no concurrent chemotherapy was administered, at least 2 weeks after completion of therapy has elapsed before enrolment, and any toxicities have resolved to grade 1 or less.
a) Prior fluoropyrimidine chemotherapy, concurrent with radiation as neoadjuvant treatment for rectal cancer is allowed.
b) Prior radiotherapy, concurrent with radiation sensitizing fluoropyrimidines in the setting of metastatic disease is allowed.
9. Adequate haematological function: ANC > 1500/µl, Platelets >75,000/µl, Haemoglobin > 8g/dl. INR and APTT <1.5 x ULN. Note: patients previously on long term anticoagulation with warfarin or low molecular weight heparin are eligible.
10. Adequate liver function: Albumin > 25 g/l. Total bilirubin <3 x ULN. AST, ALT and/or alkaline phosphatase (ALP) <5 x ULN.
11. Adequate renal function, creatinine clearance, as measured by the Cockcroft and Gault formula) of >30mls/minute.
12. Serum potassium, magnesium and total calcium < grade 2 above or below the institution’s normal limits. Note: total calcium should be corrected for albumin level as per the institution’s usual calculation method.
13. ECOG performance status 0-2.
14. Patient is being treated with non-curative intent. This may be because the disease is anatomically not resectable or that resection is contra-indicated for any reason or the patient refuses resection.
15. Archival tissue for central review of RAF/BRAF mutation status.
16. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
17. Signed, written informed consent.