MONARCC: A 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.
- Conditions
- metastatic colorectal cancerCancer - Bowel - Back passage (rectum) or large bowel (colon)
- Registration Number
- ACTRN12618000233224
- Lead Sponsor
- AGITG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 36
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.
1. Contraindications to investigational product.
2. Any prior treatment with cetuximab or panitumumab or bevacizumab.
3. Concurrent toxicity from any prior agent has not resolved to grade 1 or less.
4. Any major surgical procedure within two weeks of cycle 1 day 1.
5. Leptomeningeal disease as the only manifestation of their malignancy.
6. Known clinically significant dihydropyrimidine dehydrogenase deficiency.
7. History of interstitial lung disease or pulmonary fibrosis.
8. Untreated/active CNS metastases ie progressing, requiring ongoing corticosteroids or anticonvulsants for symptom control. Patients with CNS metastases are eligible if previously have been successfully treated with surgery and/or radiotherapy at least 8 weeks prior to cycle 1 day 1, are off all corticosteroids and/or anticonvulsants for at least 4 weeks and imaging within 4 weeks of cycle 1 day 1 excludes any progression.
9. Any other reason the investigator feels will prevent the patient from complying with the protocol specified treatments and assessments.
10. Invasive malignancy, other than CRC, diagnosed within 2 years of randomisation and that the investigator feels may have an impact on the patient’s outcome or disease assessments. Patients with prior or concurrent in-situ cervix carcinoma, skin SCC or basal cell carcinoma are eligible.
11. Other comorbidities or conditions that may compromise assessment of key outcomes
12. Life expectancy of less than 3 months.
13. Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.
14. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary endpoint is the rate of progression free survival at 6 months defined according to RECIST V1.1 criteria[ Progression free survival (PFS) is defined as the interval from date of randomisation to<br>the date of first evidence of disease progression or death, whichever occurs first. The time point for PFS is 6 months after the last patient has been enrolled ]
- Secondary Outcome Measures
Name Time Method