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BOS3: Randomized Phase II/III Trial Evaluating the Efficacy of FOLFOX Alone Versus FOLFOX Plus Aflibercept in K-ras Mutant as Perioperative Treatment in Patients With Resectable Liver Metastases From Colorectal Cancer.

Phase 2/Phase 3
18 Years
75 Years
Not Enrolling
Colorectal Cancer Metastatic, Liver Metastases, KRAS Mutated Colorectal Cancer

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Trial Information

BOS3: Randomized Phase II/III Trial Evaluating the Efficacy of FOLFOX Alone Versus FOLFOX Plus Aflibercept in K-ras Mutant as Perioperative Treatment in Patients With Resectable Liver Metastases From Colorectal Cancer.

Inclusion Criteria:

- Histologically proven CRC with 1 to 8 metachronous or synchronous liver metastases
considered to be completely resectable

- Primary tumor (or liver metastasis) of CRC must be KRAS status "mutant"

- Patients must have undergone complete resection (R0) of the primary tumor at least 4
weeks before randomization. Or for patients with synchronous metastases the primary
tumor can be resected (R0) at the same time as the liver metastases if: the patient
has a non-obstructive primary tumor and is able to receive preoperative chemotherapy
(3-4 months) before surgery1.

- Measurable hepatic disease by RECIST version 1.1

- Patients must be 18 years old or older

- A World Health Organization (WHO) performance status of 0 or 1

- Previous adjuvant chemotherapy for primary CRC is allowed if completed at least 12
months before inclusion in this study

- All the following tests should be done within 4 weeks prior to randomization:

- Hematological status: neutrophils (ANC) = 1.5x10 9/L; platelets = 100x10 9/L;
haemoglobin = 9g/dL

- Serum creatinine = 1.5 times the upper limit of normal (ULN)

- Proteinuria < 2+ (dipstick urinalysis) or =1g/24hour.

- Liver function: serum bilirubin = 1.5 x upper normal limit (ULN), alkaline
phosphatase < 5xULN

- Magnesium ≥ lower limit of normal (LLN)

- Patients with a buffer range from the normal values of +/- 5% for hematology and +/-
10% for biochemistry are acceptable. This will not apply for Renal Function,
including Creatinine.

- Women of child bearing potential (WOCBP) must have a negative serum (or urine)
pregnancy test within 14 days prior to the first dose of study treatment.

- Patients of childbearing / reproductive potential should use adequate birth control
measures, as defined by the investigator, during the study treatment period and for
at least 6 months after the last study treatment. A highly effective method of birth
control is defined as those which result in low failure rate (i.e. less than 1% per
year) when used consistently and correctly.

- Female subjects who are breast feeding should discontinue nursing prior to the first
dose of study treatment and until 6 months after the last study treatment.

- Absence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule;
those conditions should be discussed with the patient before registration in the

- Patient should be willing and able to comply with protocol requirements

- Before patient registration/randomization, written informed consent must be given
according to ICH/GCP, and national/local regulations.

Exclusion Criteria:

- Evidence of extra-hepatic metastasis (of CRC)

- Previous chemotherapy for metastatic disease or surgical treatment (e.g. surgical
resection or radiofrequency ablation) for liver metastasis. Radiotherapy alone is
allowed if given pre or post protocol treatment

- Previous exposure to VEGF/VEGFR targeting therapy within the last 12 months

- Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks
prior to randomization

- Gilbert's syndrome

- History of myocardial infarction and/or stroke within 6 months prior to randomization

- Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or
diastolic blood pressure > 100 mmHg), or history of hypertensive crisis, or
hypertensive encephalopathy

- History or evidence upon physical examination of CNS metastasis

- Bowel obstruction

- Uncontrolled hypercalcemia

- Pre-existing permanent neuropathy (NCI grade = 2)

- Known allergy to any excipient to study drugs

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression free survival

Outcome Description:

Increase in progression free survival rate at 1 year in the experimental arm (mFOLFOX6 + aflibercept) compared to mFOLFOX6 alone arm.

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Bernard Nordlinger, Pr.

Investigator Role:

Study Chair

Investigator Affiliation:

C.H.U. AMBROISE PARE AP-HP, Boulogne-Billancourt, France


Austria: Agency for Health and Food Safety

Study ID:




Start Date:

December 2012

Completion Date:

December 2016

Related Keywords:

  • Colorectal Cancer Metastatic
  • Liver Metastases
  • KRAS Mutated Colorectal Cancer
  • Liver metastases
  • Colorectal Cancer
  • KRAS mutated
  • Aflibercept
  • Randomized
  • Phase II-III
  • Perioperative treatment
  • Adjuvant
  • Neo-adjuvant
  • Surgery
  • Progression Free Survival
  • Colorectal Neoplasms
  • Neoplasm Metastasis
  • Neoplasms, Second Primary
  • Neoplasms
  • Liver Neoplasms