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Trial record 29 of 483 for:    colon cancer | ( Map: Texas, United States )

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00501410
Recruitment Status : Completed
First Posted : July 16, 2007
Last Update Posted : August 28, 2019
Bristol-Myers Squibb
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

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 or disease Intervention/treatment Phase
Colorectal Cancer Drug: 5-FU Drug: Cetuximab Drug: Dasatinib Drug: Leucovorin Drug: Oxaliplatin Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 86 participants
Intervention Model: Single Group Assignment
Masking: None (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)
Actual Study Start Date : April 23, 2007
Actual Primary Completion Date : March 3, 2017
Actual Study Completion Date : March 3, 2017

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of Dasatinib, Cetuximab and FOLFOX [ Time Frame: 2 Week Cycles ]
    If 2 or more out of the 6 patients in the cohort have dose limiting toxicity (DLT) then the prior dose level is the MTD.

Secondary Outcome Measures :
  1. Response-Rate of Dasatinib and Modified FOLFOX6 With or Without Cetuximab [ Time Frame: After 4, 14 day cycles ]
    Response and progression evaluated using a modification of the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000]. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria. Duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that recurrent disease is objectively documented.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Appendix E)
  10. Patients must have adequate organ and marrow function defined as: absolute neutrophil count (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 Cockcroft-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, international normalized ratio (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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00501410

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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
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Principal Investigator: Scott Kopetz, MD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00501410     History of Changes
Other Study ID Numbers: 2005-0842
NCI-2015-01568 ( Registry Identifier: NCI CTRP )
First Posted: July 16, 2007    Key Record Dates
Last Update Posted: August 28, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Colorectal Cancer
Dual Inhibition of EGFR
FOLFOX Chemotherapy
Folinic Acid
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Colonic Diseases
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Folic Acid
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Protein Kinase Inhibitors
Enzyme Inhibitors
Protective Agents