RAS Switch in Patients With Metastatic RAS Native Colorectal Tumors Treated With 1st Line FOLFIRI-Cetuximab

Colorectal Cancer Metastatic Clinical Trial

— BEAMING  

Official title:

Prospective, Non-Interventional Study of K-ras Status Switch in K-ras Native Patients With Metastatic Colorectal Tumors Treated With FOLFIRI-Cetuximab as First-line Treatment

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01943786
• Other study ID #: BEAMING
• Status: Active, not recruiting
• Phase: N/A
• First received: April 29, 2013
• Last updated: March 13, 2015
• Start date: April 2013
• Est. completion date: December 2015

Study information

• Verified date: March 2015
• Source: Grupo Hospital de Madrid
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Observational

Clinical Trial Summary

Adenocarcinoma of the colon and rectum is a common, serious disease and it is the second cause of death from cancer in Spain.

The prognosis of CRC depends to a great extent on its stage when diagnosed. Patients with advanced disease, who present up to 40% of all patients, have a poor prognosis. Although the application of modern chemotherapy and radiotherapy treatments obtains median survival periods of around 24 months, the proportion of patients with advanced disease who obtain a cure is low.

Systemic treatment of advanced CRC has changed considerably in the last ten years with the introduction of active drugs such as oxaliplatin, irinotecan, and capecitabine. The most commonly used first line regimens are 5-Fluorouracil-Leucovorin-Oxaliplatin (FOLFOX), Capecitabine-Oxaliplatin (XELOX), 5-Fluorouracil-Leucovorin-Irinotecan (FOLFIRI) and, to a lesser extent, Capecitabine-Irinotecan (XELIRI). Chemotherapy regimens are combined with different agents against therapeutic targets, three of which are effective in colon cancer: bevacizumab, which targets vascular endothelial growth factor (VEGF) and cetuximab or panitumumab, which target the epidermal growth factor receptor (EGFR).

The use of cetuximab and panitumumab is not recommended in patients with KRAS mutations and the combination of a VEGF and EGFR agents is not beneficial.

Two recent studies results have identified KRAS mutations as frequent drivers of acquired resistance to cetuximab and panitumumab in colorectal cancer patients. The conclusions indicate that the emergence of KRAS mutant clones can be detected non-invasively months before radiographic progression by a DNA Blood Test (Inostics´BEAMing Technology).

Centro Integral Oncológico Clara Campal (CIOCC) is aiming to undertake a pioneer project aimed at integrating the analysis of KRAS switch status by BEAMing Technology in patients with metastatic colorectal cancer, tumor KRAS wild-type and BEAMing wild-type treated with first line FOLFIRI-cetuximab

In naive chemotherapy tumor-KRAS wild-type metastatic colorectal cancer patients, who are BEAMing positive (KRAS mutated in blood) before treatment may have worse evolution in terms of PFS (progression Free Survival) and response rate than BEAMing negative (KRAS native in blood) patients.

To know the proportion of patients who are BEAMing positive (KRAS mutation can be detected in circulating extracellular DNA) at the beginning of treatment, could be of great importance for treatment efficacy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of stage IV colorectal adenocarcinoma.

• Patient = 18 years of age.

• ECOG PS 0-1

• Life expectancy = 6 months

• Candidate for first-line systemic chemotherapy according to regular clinical practice.

• Measurable disease.

• Wild-type KRAS

• Signed informed consent form.

Exclusion Criteria:

• Patient who has received prior chemotherapy for metastatic CRC, except for adjuvant treatment completed at least six months before entering study.

• Patient in whom there is a contraindication for the use of any of the drugs used in first-line treatment of colorectal cancer: 5-fluorouracil,, irinotecan or cetuximab

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Colorectal Cancer Metastatic
• Colorectal Neoplasms

Intervention

Drug:
• FOLFIRI + Cetuximab
Patients will receive study treatment (FOLFIRI + Cetuximab) according to regular clinical practice

Locations

Country	Name	City	State
Spain	Centro Integral Oncólógico Clara Campal (Madrid Norte Sanchinarro University Hospital)	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Sofia Perea, Director Clinical Trials Unit.

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To estimate the proportion of patients with advanced colorectal cancer in whom KRAS mutation can be detected in circulating extracellular DNA		Baseline	No
Secondary	To estimate the proportion of patients with metastatic colorectal cancer who switch from BEAMing negative to BEAMing positive while being treated with first line FOLFIRI-Cetuximab		At 4 months and every eight weeks until disease progression up to 12 months	No
Secondary	To estimate the response rate, in biopsy-proven K-ras wild-type patients according to KRAS status in circulating extracellular DNA.		Every eight weeks until disease progression up to 12 months	No
Secondary	Disease control rate according to KRAS status in circulating extracellular DNA.		Every eight weeks until disease progression up to 12 months	No
Secondary	Complete response rate according to KRAS status in circulating extracellular DNA.		Every eight weeks until disease progression up to 12 months	No
Secondary	Duration of response according to KRAS status in circulating extracellular DNA.	From date of first documented response until de date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months	Every eight weeks until disease progression, up to 12 months	No
Secondary	Early tumor shrinkage		At 4 months	No
Secondary	Number of each adverse event per cycle		Every 2 weeks, until end of treatment, up to 12 months	Yes