A study to explore the effects of cetuximab alone or in combination with irinotecan in patients with an abnormal gene (KRAS) in their colon cancer cells.

Phase 1

Conditions: metastatic colorectal cancer
Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05]

Registration Number: EUCTR2012-003638-18-BE

Lead Sponsor: Australasian Gastro-Intestinal Trials Group, Sydney University

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 100

Inclusion Criteria

1. Males or females with histologically confirmed colorectal cancer;
2. Age =18 yrs;
3. Metastatic disease not amenable to complete resection;
4. Measurable or evaluable disease as assessed by CT scan of the chest, abdomen and pelvis as per the RECIST v1.1 criteria;
5. Prior confirmation of tumour KRAS status as either KRAS WT (with no mutations or changes in BRAF, NRAS, PIK3CA exon20) OR KRAS G13D mutation,
6. ECOG performance status of 0-2;
7. Received and progressed on, or intolerant of all therapies listed below: (failure is defined as radiological progression during therapy, or toxicity limiting further therapy, or progression within 6 months of adjuvant treatment)
- thymidylate synthase inhibitor
- irinotecan-containing regimen
- oxaliplatin-containing regimen, OR have documented unsuitability for an oxaliplatin-containing regimen;
8. Adequate haematological and renal function;
9. Adequate liver function;
10. Life expectancy of at least 12 weeks;
11. Study treatment both planned and able to start within 14 days of randomisation;
12. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments;
13. Signed, written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion Criteria

1. Prior treatment with cetuximab or other drugs targeting the EGFR pathway;
2. Severe restrictive lung disease or radiological pulmonary findings;
3. Brain metastases that are either untreated, symptomatic, or which have not been stable for at least one month after treatment;
4. History of another malignancy within 5 years prior to registration (exception of treated cervical carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder)
5. Severe or uncontrolled cardiovascular disease;
6. Concurrent illness;
7. Presence of any psychological, familial, sociological or geographical condition;
8. Pregnancy, lactation, or inadequate contraception.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the 6 month PFS (Progression Free Survival) benefit of cetuximab alone or in combination with irinotecan in patients with KRAS WT or KRAS G13D mutated metastatic colorectal cancer (mCRC). <br>;Secondary Objective: - To determine the response rate in patients with KRAS WT or KRAS G13D mutated mCRC treated with cetuximab alone or in combination with irinotecan <br>- To determine the overall survival in patients with KRAS WT or KRAS G13D mutated mCRC treated with cetuximab alone or in combination with irinotecan <br>- To evaluate Quality of Life using the FACT-C, DLQI and FACT-EGFRI 18 questionnaires.;Primary end point(s): To determine the 6 month Progression Free Survival (PFS) benefit of cetuximab alone or in combination with irinotecan in patients with KRAS WT or KRAS G13D mutated colorectal cancer (mCRC) (PFS defined from time of randomisation to disease progression as defined by RECIST criteria version 1.1).;Timepoint(s) of evaluation of this end point: End of study

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - To determine the response rate in patients with KRAS WT or KRAS G13D mutated mCRC treated with cetuximab alone or in combination with irinotecan (Complete and Partial Responses as defined by RECIST criteria version 1.1).<br>- To determine the overall survival in patients with KRAS WT or KRAS G13D mutated mCRC treated with cetuximab alone or in combination with irinotecan (Death from any cause).<br>- To evaluate Quality of Life (as defined by worse scores on FACT-C, DLQI and FACT-EGFRI 18);Timepoint(s) of evaluation of this end point: End of study

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