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A Controlled Randomized Double-blind Multi-center Phase II Study of FOLFOX6 or FOLFIRI Combined With Sorafenib Versus Placebo in Second-line Metastatic Colorectal Carcinoma


Phase 2
18 Years
N/A
Not Enrolling
Both
Colorectal Neoplasms

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Trial Information

A Controlled Randomized Double-blind Multi-center Phase II Study of FOLFOX6 or FOLFIRI Combined With Sorafenib Versus Placebo in Second-line Metastatic Colorectal Carcinoma


Patients with metastatic CRC who received a first-line therapy with an Oxaliplatin- or
Irinotecan based Fluoropyrimidine containing regimen ± bevacizumab and had a progression
subsequently, are eligible for this study. Patients will be randomized to receive
chemotherapy (FOLFOX6 or FOLFIRI) + sorafenib 400 mg bid or chemotherapy + placebo. Patients
who have received an Oxaliplatin based Fluoropyrimidine containing regimen in first-line
will obtain FOLFIRI during this study. Patients who have received an Irinotecan based
Fluoropyrimidine containing regimen in first-line will obtain FOLFOX6.

Primary objective of the study is to compare the Progression-free-survival (PFS) between
patients receiving chemotherapy (FOLFOX6 or FOLFIRI) + sorafenib with chemotherapy +
placebo.


Inclusion Criteria:



- Age > 18 years.

- ECOG Performance Status of 0 to 2

- Life expectancy of at least 12 weeks.

- Subjects with at least one uni-dimensional (RECIST) measurable lesion of metastatic
colorectal carcinoma after first-line chemotherapy with an Oxaliplatin- or Irinotecan
based Fluoropyrimidine containing regimen ± bevacizumab and had a progression
subsequently. Lesions must be measured by CT-scan or MRI.

- Adequate bone marrow, liver and renal function as assessed by the following
laboratory requirements to be conducted within 7 days prior to screening:

- Hemoglobin > 9.0 g/dl

- Absolute neutrophil count (ANC) >1,500/mm3

- Platelet count 100,000/μl Total bilirubin < 1.5 times the upper limit of normal

- ALT and AST < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients
with liver involvement of their cancer)

- Alkaline phosphatase < 4 x upper limit of normal

- PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically
anticoagulated with an agent such as coumadin or heparin will be allowed to
participate provided that no prior evidence of underlying abnormality in these
parameters exists.]

- Serum creatinine < 1.5 x upper limit of normal

- Signed and dated informed consent before the start of specific protocol procedures

Exclusion Criteria:

- History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI
more than 6 mo prior to study entry is allowed); cardiac arrythmias requiring
anti-arrythmic therapy (beta blockers or digoxin are permitted) or uncontrolled
hypertension

- History of HIV infection or chronic hepatitis B or C

- Active clinically serious infections (> grade 2 NCI-CTC version 3.0)

- Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months
from definitive therapy, has a negative imaging study within 4 weeks of study entry
and is clinically stable with respect to the tumor at the time of study entry)

- Patients with seizure disorder requiring medication (such as steroids or
anti-epileptics)

- History of organ allograft

- Patients with evidence or history of bleeding diathesis

- Patients undergoing renal dialysis

- Known deficit in Dihydropyrimidine Deshydrogenase (DPD)

- Contraindications for the use of atropine in patients receiving FOLFIRI

- Previous or concurrent cancer that is distinct in primary site or histology from the
cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal
cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively
treated > 3 years prior to study entry.

- Peripheral sensory neuropathy > CTC grade 2

- Chronic inflammatory bowel disease; ileus; genetic fructose intolerance

- Pregnant or breast-feeding patients.

- Women of childbearing potential must have a negative pregnancy test performed within
7 days before the start of treatment. Fertile women and men (<2 years after last
menstruation in women) must use effective means of contraception (intrauterine
contraceptive device, contraceptive implants, injectables (hormonal depot),
transdermal hormonal contraception (contraceptive patch), sexual abstinence or
vasectomised partner) during treatment and for at least 6 months after last
administration of medication.

- Substance abuse, medical, psychological or social conditions that may interfere with
the patient‟s participation in the study or evaluation of the study results

- Any condition that is unstable or could jeopardize the safety of the patient and
their compliance in the study 18. Patients unable to swallow oral medications.

- Any other anticancer chemotherapy or immunotherapy during the study or within 4 weeks
of study entry.

- Radiotherapy during study or within 3 weeks of start of study drug. (Palliative
radiotherapy will be allowed). Major surgery within 4 weeks of start of study

- Autologous bone marrow transplant or stem cell rescue within 4 months prior to study
treatment

- Use of biologic response modifiers, such as G-CSF, within 3 week of study entry.
[G-CSF and other hematopoietic growth factors may be used in the management of acute
toxicity such as febrile neutropenia when clinically indicated or at the discretion
of the investigator, however, they may not be substituted for a required dose
reduction.] [Patients taking chronic erythropoietin are permitted provided no dose
adjustment is undertaken within 2 months prior to the study or during the study]

- Investigational drug therapy outside of this trial during or within 4 weeks of study
entry

- Prior exposure to the study drug.

- Any St. John´s wort containing remedy

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

To compare the PFS between patients receiving chemotherapy (FOLFOX6 or FOLFIRI) + sorafenib with chemotherapy + placebo

Outcome Time Frame:

6 to 12 months

Safety Issue:

No

Principal Investigator

Thomas Höhler, Prof. Dr. med.

Investigator Role:

Principal Investigator

Authority:

Germany: Federal Institute for Drugs and Medical Devices

Study ID:

AIO KRK 0307

NCT ID:

NCT00889343

Start Date:

March 2009

Completion Date:

December 2012

Related Keywords:

  • Colorectal Neoplasms
  • Second-line therapy of metastatic colorectal cancer
  • Sorafenib
  • Colorectal Neoplasms
  • palliative therapy
  • after progression of firstline therapy with an Oxaliplatin- or Irinotecan based Fluoropyrimidine containing regimen ± bevacizumab
  • Neoplasms
  • Colorectal Neoplasms

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