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FOLFOX Chemotherapy Regimen (5-FU, Leucovorin, Oxaliplatin) in Metastatic Colorectal Cancer
This study is currently recruiting participants.
Verified by M.D. Anderson Cancer Center, February 2009
First Received: July 12, 2007   Last Updated: February 18, 2009   History of Changes
Sponsors and Collaborators: M.D. Anderson Cancer Center
Bristol-Myers Squibb
Information provided by: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00501410
  Purpose

Primary Objectives:

  • To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combination of dasatinib, cetuximab and modified FOLFOX6 in adult patients with metastatic colorectal cancer.
  • To demonstrate biological activity of the combination regimen on c-Src activity at the MTD in the expansion cohort.

Secondary Objectives:

  • To demonstrate the feasibility of peripheral blood biomarkers of Src inhibition.
  • To determine the safety profile and tolerability of this regimen in this patient population;
  • To document the antitumor effects of this regimen in this patient population.

Condition Intervention Phase
Colorectal Cancer
Drug: 5-FU
Drug: Cetuximab
Drug: Dasatinib
Drug: Leucovorin
Drug: Oxaliplatin
Phase I

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: Dual Inhibition of EGFR and c-Src by Cetuximab and Dasatinib Combined With FOLFOX Chemotherapy in Metastatic Colorectal Cancer (CA180048)

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • To study the highest tolerable dose of a combination of dasatinib, cetuximab and FOLFOX (5-fluorouracil [5-FU], leucovorin [LV], and Eloxatin [oxaliplatin]) that can be given to patients with metastatic colorectal cancer. [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 42
Study Start Date: April 2007
Estimated Study Completion Date: April 2009
Estimated Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
FOLFOX + Dasatinib + Cetuximab
Drug: 5-FU
400 mg/m^2 by vein push on Day 1, Followed by 2400 mg/m^2 by vein over 46 Hours On Days 1 & 2.
Drug: Cetuximab
Initial Dose = 400 mg/m^2 by vein, then 250 mg/m^2 Weekly On Days 1 & 8
Drug: Dasatinib
100 mg by mouth daily on days 1-14.
Drug: Leucovorin
400 mg/m^2 by vein on day 1.
Drug: Oxaliplatin
85 mg/m^2 by vein on day 1.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient must have histologically or cytologically confirmed colorectal adenocarcinoma with metastatic disease documented on diagnostic imaging studies
  2. Patient must have wild type KRAS.
  3. Patient must have previously progressed, either clinically or radiographically, on systemic therapy for metastatic colorectal cancer, with no limit on the number of prior regimens.
  4. For the expansion cohort, only patients with liver metastases >/= 2.0 cm amenable to percutaneous CT or U/S guided biopsy and who agree to having 2 liver biopsies done are eligible.
  5. Written informed consent obtained.
  6. Age >/= 18 years to provide a uniform oncologic phenotype of adult-onset colorectal cancer.
  7. ECOG performance status 0-1
  8. Patients must have adequate organ and marrow function defined as: ANC >/= 1,500/mm^3; platelets >/= 100,000/ mm^3; hemoglobin >/= 9 gm/dL (may be transfused to maintain or exceed this level); total bilirubin </= 1.5 mg/dL; AST (SGOT)/ALT(SGPT) </= 2.5 times institution's upper limit of normal (IULN), or </= 5 times IULN if known liver metastases; serum creatinine < 2.0 mg/dL
  9. Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the start of study medications.

Childbearing potential is defined as a woman who is not post-menopausal for 12 months or longer or is not surgically sterile. Patients must agree to practice acceptable contraceptive methods.

Exclusion Criteria:

  1. Recent (within 4 weeks of the first infusion of study drugs on this study), or planned participation in another experimental therapeutic drug study.

    Patients who have had any systemic chemotherapy, radiotherapy, or major surgery within 28 days prior to the first infusion of study drugs.

  2. Patients who have not recovered to </= grade 2 for neuropathy or </= grade 1 for other side effects due to prior treatment.
  3. Patients with known brain metastases because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  4. Female patients who are pregnant or lactating or men and women of reproductive potential not willing to employ an effective method of birth control during treatment and for 3 weeks after discontinuing study treatment
  5. Patients with known dihydropyrimidine dehydrogenase deficiency.
  6. Patients with a history of significant bleeding disorder unrelated to cancer, including: Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease); Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
  7. Patients currently taking the following drugs that are generally accepted to have a risk of causing Torsades de Pointes:haloperidol, methadone, amiodarone, sotalol, erythromycins, clarithromycin cisapride, chlorpromazine, bepridil, droperidol, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine, quinidine, procainamide, disopyramide, ibutilide, dofetilide. Subjects who have discontinued any of these medications must have a wash-out of at least 5 days (or 14 days for amiodarone) prior to the first dose of dasatinib.
  8. Patients with a history of allergic reactions attributed to cetuximab, oxaliplatin, 5-FU, or leucovorin.
  9. Current use of full-dose warfarin (except as required to maintain patency of preexisting, permanent indwelling IV catheters). For subjects receiving warfarin for catheter patency, INR should be < 1.5.
  10. Current or recent (<2 week) use of aspirin (at a dose greater than 81 mg/day) or clopidogrel.
  11. Diagnosed or suspected congenital long QT syndrome
  12. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes).
  13. Previous allergic reaction to a human monoclonal antibody.
  14. Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec) on both the Fridericia [QTc = QT/RR^1/3] and Bazett's [QTc = QT/sqrtRR] correction. Bazett's correction is calculated automatically by institutional EKG machines
  15. Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: Uncontrolled high blood pressure (systolic blood pressure >/= 140 and diastolic blood pressure >/= 90), history of labile hypertension, or history of poor compliance with an antihypertensive regimen. Unstable angina or stable angina markedly limiting ordinary physical activity. (Angina occurs on walking one to two blocks on the level and climbing one flight of stairs in normal conditions and at a normal pace) .
  16. Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: New York Heart Association (NYHA) >/= grade 2 congestive heart failure; Myocardial infarction within 6 months of study enrollment; History of stroke within 6 months of study enrollment; Unstable symptomatic arrhythmia requiring medication (Patients with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal SVT are eligible); Clinically significant peripheral vascular disease; Uncontrolled diabetes; Serious active or uncontrolled infection
  17. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of a study drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications
  18. Inability to take oral medications.
  19. Inability to comply with study and/or follow-up procedures
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00501410

Contacts
Contact: Scott Kopetz, MD 713-792-2828

Locations
United States, Texas
U.T.M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Scott Kopetz, MD            
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
Investigators
Principal Investigator: Scott Kopetz, MD U.T.M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: U.T.M.D. Anderson Cancer Center ( Scott Kopetz, MD/Assistant Professor )
Study ID Numbers: 2005-0842
Study First Received: July 12, 2007
Last Updated: February 18, 2009
ClinicalTrials.gov Identifier: NCT00501410     History of Changes
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Colorectal Cancer
Dual Inhibition of EGFR
FOLFOX Chemotherapy
5-FU
Cetuximab
Dasatinib
Leucovorin
Oxaliplatin
5-Fluorouracil
BMS-354825
Eloxatin
Sprycel
C225
Erbitux
IMC-C225
Adrucil
Efudex
Folinic Acid

Study placed in the following topic categories:
Antimetabolites
Immunologic Factors
Gastrointestinal Diseases
Colonic Diseases
Leucovorin
Folate
Rectal Diseases
Protein Kinase Inhibitors
Vitamin B9
Oxaliplatin
Dasatinib
Vitamins
Micronutrients
Digestive System Neoplasms
Vitamin B Complex
Cetuximab
Trace Elements
Intestinal Diseases
Folinic Acid
Immunosuppressive Agents
Intestinal Neoplasms
Folic Acid
Digestive System Diseases
Fluorouracil
Gastrointestinal Neoplasms
Colorectal Neoplasms

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Gastrointestinal Diseases
Antineoplastic Agents
Colonic Diseases
Physiological Effects of Drugs
Leucovorin
Protein Kinase Inhibitors
Rectal Diseases
Oxaliplatin
Neoplasms by Site
Vitamins
Dasatinib
Therapeutic Uses
Micronutrients
Vitamin B Complex
Digestive System Neoplasms
Growth Substances
Cetuximab
Enzyme Inhibitors
Intestinal Diseases
Immunosuppressive Agents
Intestinal Neoplasms
Pharmacologic Actions
Neoplasms
Digestive System Diseases
Fluorouracil
Gastrointestinal Neoplasms

ClinicalTrials.gov processed this record on July 06, 2009