FOLFOX Chemotherapy Regimen (5-FU, Leucovorin, Oxaliplatin) in Metastatic Colorectal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00501410
First received: July 12, 2007
Last updated: January 3, 2014
Last verified: January 2014
  Purpose

The goal of the Phase I part of this clinical research study is to find 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. The safety of these drugs in combination will also be studied.

The goal of the Phase II part of this clinical research study is to learn if dasatinib given in combination with FOLFOX with or without cetuximab can help to control metastatic colorectal cancer.


Condition Intervention Phase
Colorectal Cancer
Drug: 5-FU
Drug: Cetuximab
Drug: Dasatinib
Drug: Leucovorin
Drug: Oxaliplatin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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:
  • Maximum Tolerated Dose (MTD) of Dasatinib, Cetuximab and FOLFOX [ Time Frame: 2 Week Cycles ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Dose Limiting Toxicity (DLT) of Dasatinib, Cetuximab and FOLFOX [ Time Frame: 2 Week Cycles ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 83
Study Start Date: April 2007
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FOLFOX + Dasatinib + Cetuximab
5-FU 2400 mg/m^2 by vein over 46 Hours On Days 1 & 2. Cetuximab initial dose = 400 mg/m^2 by vein, then 250 mg/m^2 Weekly On Days 1 & 8. Dasatinib 100 mg by mouth daily on days 1-14. Leucovorin 400 mg/m^2 by vein on day 1. Oxaliplatin 85 mg/m^2 by vein on day 1.
Drug: 5-FU
2400 mg/m^2 by vein over 46 Hours On Days 1 & 2.
Other Name: 5-Fluorouracil
Drug: Cetuximab
Initial Dose = 400 mg/m^2 by vein, then 250 mg/m^2 Weekly On Days 1 & 8
Drug: Dasatinib
Starting dose level: 100 mg by mouth daily on days 1-14.
Other Name: BMS-354825
Drug: Leucovorin
400 mg/m^2 by vein on day 1.
Other Name: Folinic Acid
Drug: Oxaliplatin
85 mg/m^2 by vein on day 1.
Other Name: Eloxatin

  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. Phase IB: Patient must have wild type KRAS.
  3. Phase IB: 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.
  4. Phase II: Patient must have known KRAS (exon 1, codon 12, 13) or sufficient available tumor tissue from the primary tumor or metastatic site for KRAS mutation analysis [Phase II only].
  5. Patient must have previously progressed on systemic therapy for metastatic colorectal cancer, with no limit on the number of prior regimens. For patients in the Phase II cohort, they must have progressed on 5-FU or capecitabine and oxaliplatin [patients with KRAS mutated tumors], and either cetuximab or panitumumab [patients with KRAS wild type tumors].
  6. (Continued from # 5) The following criteria must be met for progression. • Baseline imaging was performed 1 month or less prior to starting regimen. • Average treatment intensity (number of cycles received/number of cycles anticipated in absence of delays) of greater than 70%. • Restaging study demonstrating progression 6 weeks or less from last dose of oxaliplatin and EGFR inhibitor (if applicable). • Progression may be by RECIST criteria or, with PI approval, clinical progression.
  7. Written informed consent obtained
  8. Age >/= 18 years to provide a uniform oncologic phenotype of adult-onset colorectal cancer.
  9. ECOG performance status 0-1 (Appendix E)
  10. 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; · Creatinine clearance > 60mL/min using Cockroft-Gault formula.
  11. 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 as outlined in the protocol.

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 21 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 radiographic evidence of pleural effusions in the last 30 days prior to enrollment.
  4. 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.
  5. 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
  6. Patients with known dihydropyrimidine dehydrogenase deficiency.
  7. 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)
  8. 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.
  9. Patients with wild type KRAS tumors with a history of allergic reactions attributed to cetuximab, oxaliplatin, 5-FU, capecitabine, or leucovorin that, previously, have not been adequately prevented with premedications.
  10. 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.
  11. Current or recent (<2 week) use of aspirin (at a dose greater than 81 mg/day) or clopidogrel.
  12. Diagnosed or suspected congenital long QT syndrome
  13. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes).
  14. Previous allergic reaction to a human monoclonal antibody.
  15. 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
  16. 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) .
  17. 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
  18. 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
  19. Inability to take oral medications.
  20. Inability to comply with study and/or follow-up procedures.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00501410

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

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00501410     History of Changes
Other Study ID Numbers: 2005-0842
Study First Received: July 12, 2007
Last Updated: January 3, 2014
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

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

ClinicalTrials.gov processed this record on September 18, 2014