A randomised phase II study evaluating Dual inhibition of epidermal growth factor receptor (EGFR) signalling using CetUXimab and Erlotinib or dose escalated Cetuximab in patients with chemotherapy refractory KRAS wild-type metastatic colorectal cancer

Phase 2

• Conditions: Metastatic colorectal cancer; EGFR inhibitor induced skin toxicity; Cancer - Bowel - Back passage (rectum) or large bowel (colon); Skin - Other skin conditions

• Registration Number: ACTRN12611001142921
• Lead Sponsor: Australasian Gastrointestinal Trials Group (AGITG)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-11-01
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Stopped early
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

1. Males or females with histologically confirmed colorectal cancer.
2. Age greater than or equal to 18 yrs.
3. Metastatic disease not amendable to resection, as confirmed by the investigator.
4. Metastatic disease which is assessable by CT scan using RECIST v1.1 criteria.
5. KRAS wild type tumour status, confirmed by means of mutation analysis performed on representative samples of diagnostic tumour tissue.
6. Received and failed fluoropyrimidine therapy, where failure is defined as radiological progression after therapy for metastatic disease, prior adjuvant therapy, or toxicity limiting further therapy.
7. Received and failed oxaliplatin therapy, where failure is defined as radiological progression after therapy for metastatic disease, prior adjuvant therapy, or toxicity limiting further therapy.
8. Received and failed irinotecan therapy, where failure is defined as radiological progression after therapy for metastatic disease or toxicity limiting further therapy.
9. ECOG performance status of 0 or 1.
10. Adequate bone marrow function with platelets >100 X 10^9/l and ANC > 1.5 X 10^9/l.
11. Adequate renal function (creatinine clearance >40 ml/min using the Cockcroft Gault formula.
12. Adequate hepatic function (serum bilirubin < 1.25 X ULN, and either ALT or AST <2.5 X ULN (or <5 X ULN if liver metastases present).
13. Life expectancy of at least 12 weeks.
14. Study treatment both planned and able to start within 14 days of randomisation.
15. Willing and able to comply with all study requirements, including treatment (e.g. able to swallow tablets), timing and/or nature of required assessments.
16. Signed, written informed consent.

Exclusion Criteria

1. Prior treatment with drugs targeting EGFR such as Cetuximab, Panitumumab or Erlotinib.
2. Participation in any investigational drug study within 4 weeks prior to planned study treatment start date.
3. Patients with uncontrolled clinically significant cardiac disease, arrhythmias or angina pectoris.
4. Untreated CNS metastases.
5. Other concurrent uncontrolled medical conditions.
6. Other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer treated with curative intent >2 years previously without evidence of relapse.
7. Patients with a tetracycline allergy will be excluded from the second randomisation only.
8. Pregnancy, lactation, or inadequate contraception. Women must be post menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to the first randomisation. Men must have been surgically sterilised or use a (double if required) barrier method of contraception.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Tumour response rate, as assessed by RECIST v.1.1 using chest, abdomen and pelvis CT.[Baseline, 6-weekly while on treatment then 3-monthly for 12 months of follow-up. <br><br>RECIST assessments cease for completion of follow-up, study withdrawal, progressive disease, new anti-cancer therapy or patient death.]