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

NCT00501410 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2005-0842NCI-2015-01568
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Dasatinib, Cetuximab and FOLFOX

  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.

  2 Week Cycles

Secondary Outcomes (1)

• Response-Rate of Dasatinib and Modified FOLFOX6 With or Without Cetuximab

  After 4, 14 day cycles

Study Arms (1)

FOLFOX + Dasatinib + Cetuximab

EXPERIMENTAL

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; Drug: Cetuximab; Drug: Dasatinib; Drug: Leucovorin; Drug: Oxaliplatin

Interventions

5-FU DRUG

2400 mg/m\^2 by vein over 46 Hours On Days 1 \& 2.

Also known as: 5-Fluorouracil

FOLFOX + Dasatinib + Cetuximab

Cetuximab DRUG

Initial Dose = 400 mg/m\^2 by vein, then 250 mg/m\^2 Weekly On Days 1 \& 8

FOLFOX + Dasatinib + Cetuximab

Dasatinib DRUG

Starting dose level: 100 mg by mouth daily on days 1-14.

Also known as: BMS-354825

FOLFOX + Dasatinib + Cetuximab

Leucovorin DRUG

400 mg/m\^2 by vein on day 1.

Also known as: Folinic Acid

FOLFOX + Dasatinib + Cetuximab

Oxaliplatin DRUG

85 mg/m\^2 by vein on day 1.

Also known as: Eloxatin

FOLFOX + Dasatinib + Cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have histologically or cytologically confirmed colorectal adenocarcinoma with metastatic disease documented on diagnostic imaging studies
• Phase IB: Patient must have wild type KRAS.
• 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.
• 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 \[Phase II only\].
• 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 \[patients with KRAS wild type tumors\].
• (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.
• Written informed consent obtained
• Age \>/= 18 years to provide a uniform oncologic phenotype of adult-onset colorectal cancer.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Appendix E)
• 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.
• 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.

You may not qualify if:

• 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.
• Patients who have not recovered to \</= grade 2 for neuropathy or \</= grade 1 for other side effects due to prior treatment.
• Patients with radiographic evidence of pleural effusions in the last 30 days prior to enrollment.
• 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.
• 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
• Patients with known dihydropyrimidine dehydrogenase deficiency.
• 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)
• 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.
• 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.
• 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.
• Current or recent (\<2 week) use of aspirin (at a dose greater than 81 mg/day) or clopidogrel.
• Diagnosed or suspected congenital long QT syndrome
• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes).
• Previous allergic reaction to a human monoclonal antibody.
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Fluorouracil; Cetuximab; Dasatinib; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes

Study Officials

• Scott Kopetz, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2007
• First Posted: July 16, 2007
• Study Start: April 23, 2007
• Primary Completion: March 3, 2017
• Study Completion: March 3, 2017
• Last Updated: August 28, 2019

Record last verified: 2019-08

Locations

US (1)