Can extra tests on cancer samples identify more patients with bowel/colon cancer who should be treated with drugs called anti-EGFR agents?

Phase 4

• Conditions: Advanced colorectal cancer; Cancer

• Registration Number: ISRCTN11061442
• Lead Sponsor: niversity of Leeds

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-11-30
• Last Update Posted: 21 May 2024
• Study Completion: 2026-03-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 440

Inclusion Criteria

Current inclusion criteria as of 30/04/2024:
Inclusion criteria for registration:
1. Age >=18 years
2. Biopsy-confirmed adenocarcinoma of the colon with a right primary tumour location (defined as proximal to and including the splenic flexure)
3. aCRC defined as either M1 or locally inoperable disease.
4. Tumour RAS status either wild-type ( by local testing) or unknown
5. Tumour measurable by RECIST v1.1 criteria on CT scan (scans are not required to be reported to RECIST at site)
6. Pre-registration laboratory tests:
6.1. Neutrophils >=1.5 x10^9/l and platelet count >=100 x10^9/l
6.2. Serum bilirubin <=1.25 x upper limit of normal (ULN), alkaline phosphatase < = 5x ULN, and serum transaminase (either AST or ALT) <=2.5 x ULN
6.3. Estimated creatinine clearance >=50ml/min
7. Medically fit for the trial treatments
8. Sufficient tumour material for EREG/AREG analysis
9. Written informed consent for registration

Inclusion criteria for randomisation:
1. Registered in ARIEL
2. ARIEL central or local testing confirms tumour RAS-wt status
3. ARIEL central testing confirms tumour EREG/AREG high
4. Patients have had CT scan within the timeframes stipulated in the protocol. (If there is a contrast reaction, then non-contrast CT with MRI is acceptable assuming at least one of these modalities shows measurable disease at baseline for ETS evaluation and both modalities are repeated at the two trial timepoints at weeks 8 and 16.)
5. WHO performance status (PS) 0, 1 or 2
6. For women of childbearing potential, negative pregnancy test as per standard practice and adequate contraceptive precautions.
7. Effective contraception for male patients if the risk of conception exists.
8. Fit for combination chemotherapy plus cetuximab/panitumumab
9. Written informed consent for randomisation

Previous inclusion criteria:
Inclusion criteria for registration:
1. Age >=18 years
2. Biopsy-confirmed adenocarcinoma of the colon with a right primary tumour location
3. aCRC defined as either M1 or locally inoperable disease.
4. Tumour RAS status either wild-type ( by local testing) or unknown
5. Tumour measurable by RECIST v1.1 criteria
6. Pre-registration laboratory tests:
6.1. Neutrophils >=1.5 x10^9/l and platelet count >=100 x10^9/l
6.2. Serum bilirubin <=1.25 x upper limit of normal (ULN), alkaline phosphatase < = 5x ULN, and serum transaminase (either AST or ALT) <=2.5 x ULN
6.3. Estimated creatinine clearance >=50ml/min
7. Medically fit for the trial treatments
8. Sufficient tumour material for EREG/AREG analysis
9. Written informed consent for registration

Inclusion criteria for randomisation:
1. Registered in ARIEL
2. ARIEL central or local testing confirms tumour RAS-wt status
3. ARIEL central testing confirms tumour EREG/AREG high
4. Patients have had CT scan within the timeframes stipulated in protocol
5. WHO performance status (PS) 0, 1 or 2
6. For women of childbearing potential, negative pregnancy test as per standard practice and adequate contraceptive precautions.
7. Effective contraception for male patients if the risk of conception exists.
8. Fit for combination chemotherapy plus cetuximab/panitumumab
9. Written informed consent for randomisation

Exclusion Criteria

Exclusion criteria for registration:
1. Tumour RAS-mutation present
2. Prior chemotherapy for mCRC (may have received neoadjuvant or adjuvant chemotherapy provided disease did not progress on treatment, and > 6 months since last dose)
3. Prior anti-EGFR agent therapy

Exclusion criteria for randomisation:
1. Patient has received more than one cycle of chemotherapy since registration
2. Women who are breastfeeding
3. Patients with history of hypersensitivity to irinotecan, oxaliplatin, 5-fluorouracil or any of their excipients
4. Patients in receipt of live vaccine within four weeks prior to randomisation.
5. Patients with a history interstitial pneumonitis/idiopathic lung disease (ILD)
6. Patients with a history of keratitis, ulcerative keratitis or severe dry eye
7. Patients with a history of severe skin reaction which in the clinicians opinion could be exacerbated by EGFR Mab (cf Steven’s Johnson Syndrome)

Study & Design

• Study Type: Interventional
• Study Design: Not specified