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Single-Arm, Multicenter, Prospective, Phase 2 Study for the Evaluation of Biomarkers in Patients With Advanced &/or Metastatic Colorectal Cancer With Wild Type KRAS Treated Biweekly With Chemotherapy and Cetuximab as First-Line Treatment

Phase 2
18 Years
Open (Enrolling)
Colorectal Cancer

Thank you

Trial Information

Single-Arm, Multicenter, Prospective, Phase 2 Study for the Evaluation of Biomarkers in Patients With Advanced &/or Metastatic Colorectal Cancer With Wild Type KRAS Treated Biweekly With Chemotherapy and Cetuximab as First-Line Treatment

Inclusion Criteria:

- Male or female, age ≥ 18 years

- Able to sign an informed consent form

- Advanced and/or metastatic colorectal cancer

- Colorectal cancer with KRAS wild type genotype

- At least one unidimensionally measurable lesion according to RECIST criteria (1.1
revised) (to be assessed ≤ 28 days prior to the study treatment)

- All patients with the following features will be included:

1. Progression free survival > 6 months after adjuvant treatment +/- radiotherapy

2. "De novo" diagnosis of the disease

- Performance ECOG status of 0-2

- Life expectancy ≥ 3 months

- Adequate bone marrow function: neutrophils ≥1,5 x 10^9/L; platelets ≥ 100 x 10^9/L;
hemoglobin ≥9 g/dL.

- Adequate liver, renal and hematological function as follows:

1. Adequate liver function: SGOT and SGPT 2.5 x ULN (5 x ULN in case of hepatic
metastasis). Total bilirubin < 1,5 x ULN. Alkaline phosphatase 2,5 x LSN (5 x
ULN if hepatic metastasis or 10 x ULN if bone metastasis)

2. Creatinine clearance or creatinine clearance during 24 hours ≥ 50 mL/min

3. Magnesium ≥ LLN, calcium ≥ LLN

Exclusion Criteria:

- PS > 2 or elderly patients with fragility criteria

- Previous surgery for metastasis

- Previous systemic treatment for the metastatic colorectal cancer

- Previous treatment with antibodies anti-EGFR or treatment with small-molecule EGFR
tyrosine kinase inhibitors or EGFR signal transduction inhibitors. Subjects who
suspend their first dose due to a reaction to the infusion can participate

- Central nervous system metastasis (except: treated subjects with asymptomatic CNS
metastasis who have not received steroids within the 30 days prior to inclusion)

- Prior malignant tumor in the last 5 years, except: basal cell carcinoma of the skin
or pre-invasive cervical cancer

- Unresolved toxicities from a prior systemic treatment which do not qualify the
patient for inclusion

- Presence of peripheral neuropathy (degree > 1 in the ctc version 3.0) and serious
nonhealing wound, ulcer, or bone fracture

- Hormonal treatment, immunotherapy or experimental or approved antibodies/proteins ≤
30 days before the inclusion

- Uncontrolled serious cardiovascular disease or: congestive cardiac failure NYHA lll
or lV, unstable angina pectoris, myocardial infarction precedents in the past 12
months, significant arrhythmias

- Interstitial pneumonitis or pulmonary fibrosis precedents, or interstitial
pneumonitis or pulmonary fibrosis signs on the thoracic CT-scan

- Treatment for systemic infection within the 14 days prior to treatment

- Acute/subacute intestinal occlusion and/or active inflammatory bowel disease or any
other bowel disease producing chronic diarrhea

- Precedent of Gilbert's syndrome or dihydropyrimidine dehydrogenase deficiency

- Precedent of any disease which can increase the risks associated to the participation
in the study or interfere in the study results

- Known positive test for the following infections: HIV, Hepatitis C + abnormal liver
enzymes values, active chronic Hepatitis B (except Hepatitis C seropositive with
normal liver enzymes)

- All concurrent diseases which can increase the toxicity risk

- The individual presents a disorder of any kind which jeopardizes their ability to
give their written consent form and/or fulfill the study procedures

- Any investigational agent within 30 days before enrolment

- Pregnant or breastfeeding woman, or planning to get pregnant within the 6 months
after treatment

- Surgery (excluding the diagnostic biopsy or placing of a central venous catheter)

- Woman or man of childbearing potential not consenting to use adequate contraceptive
precautions during the study and 6 months after de last administration for women, and
1 month for men

- Unability to fulfill the study requirements by the patients

- Psychological, family, sociological or geographical conditions that may interfere
with the fulfillment of the study protocol and the follow-up calendar

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Screening

Outcome Measure:

Progression free survival

Outcome Description:

Measurements according to RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors). Main techniques: CT-scan. Two groups will be defined based on the score built from the proposed clinical variables and biomarkers. Instead of a binomial distribution, a Log-rank method has been used to calculate the sample size in order to include all the incidents during the follow-up. Expecting a minimum 20% difference (60 vs. 40%) on PFS at 12 months between groups and with the following assumptions: Alpha error (bilateral): 5% Beta error: 20%

Outcome Time Frame:

anticipated: 4 years

Safety Issue:


Principal Investigator

Jesús García Foncillas, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Grupo Espanol Multidisciplinario del Cancer Digestivo


Spain: Agencia Española de Medicamentos y Productos Sanitarios

Study ID:




Start Date:

January 2011

Completion Date:

December 2014

Related Keywords:

  • Colorectal Cancer
  • colorectal cancer
  • advanced
  • metastatic
  • KRAS
  • biomarkers (BRAF, IGF1P/MMp7,PI3K-PTEN)
  • cetuximab
  • Colorectal Neoplasms