None listed
Conditions
Brief summary
This study aims to determine the safety and efficacy of three different anti-cancer treatments in patients with colorectal cancer which has not responded to chemotherapy. Who is it for? You may be eligible to join this study if you are aged 18 years or more and have colorectal cancer which is metastatic (i.e. has spread) and which has not responded to prior chemotherapy treatment. Patients with this health history routinely have a test performed on their cancer cells for a mutation in a gene called KRAS. Participants must have the non-mutated ('wild-type') variant of the KRAS gene to be eligible, among other health related criteria. Trial details Participants in this trial will be randomly (by chance) allocated to one of three arms (groups). Participants in Arm A will receive the standard dose of a drug called Cetuximab, which will be administered weekly by intravenous infusion (i.e. by a needle into the vein). Participants in Arm B will undergo the same treatment with Cetuximab, but will also take daily Erlotinib via an oral tablet (or tablets). Participants in Arm C will receive high dose Cetuximab on a weekly basis. Participants will also have the option to participate in an additional skin management study looking at 2 skin treatment options that might reduce some of the skin side effects commonly experienced by patients receiving these kinds of anti-cancer therapy. Patients participating in the skin management component will be randomly allocated to either of the 2 options. All participants will be assessed on a regular basis for the duration of their treatment, then for at least 12 months afterwards to determine response to treatment, safety and quality of life. It is not certain how long treatment will continue, as it is planned to be given until either the cancer progresses, or makes you feel too sick, or you indicate that you no longer want to participate, or you decide with your study doctor that there is no benefit to continuing treatment.
Interventions
Patients randomised to treatment Arm B will receive dual EGFR inhibition, consisting of Cetuximab 400mg/m2 (initial dose), then 250mg/m2 via intravenous infusion each week, plus Erlotinib 100mg via oral tablet(s) daily continuously.
Patients randomised to treatment Arm C will receive high-dose Cetuximab, 500mg/m2 via intravenous infusion each week.
Treatment will continue until disease progression, unacceptable toxicity (as defined in the protocol), patient and/or clinician preference, or pati
Patients randomised to treatment Arm B will receive dual EGFR inhibition, consisting of Cetuximab 400mg/m2 (initial dose), then 250mg/m2 via intravenous infusion each week, plus Erlotinib 100mg via oral tablet(s) daily continuously. Patients randomised to treatment Arm C will receive high-dose Cetuximab, 500mg/m2 via intravenous infusion each week. Treatment will continue until disease progression, unacceptable toxicity (as defined in the protocol), patient and/or clinician preference, or patient death. Patients participating in the optional skin management study randomised to Group 1 will commence pre-emptive skin side effect treatments the day before starting study Cetuximab, and will continue until study treatment is ceased. Patients will be required to adhere to: daily use of moisturiser and topical 1% hydrocortisone (steroid) applied to face, hands, feet, neck, back each day; use of sunscreen before sun exposure; and taking doxycycline (antibiotic) 100mg via oral tablet(s) twice each day.
Sponsors
Australasian Gastrointestinal Trials Group (AGITG)
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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.
Outcome results
None listed