Clinical Trials /

A Trial of mFOLFIRI With MEK162 in Patients With Advanced KRAS Positive Metastatic Colorectal Cancers

NCT02613650

Description:

This is a Phase 1b, open label, dose-finding study to determine the Maximum Tolerated Dose (MTD) of MEK162 in combination with mFOLFIRI, and to evaluate the response rate, clinical benefit rate and additional safety parameters of the treatment combination

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Trial of mFOLFIRI With MEK162 in Patients With Advanced KRAS Positive Metastatic Colorectal Cancers
  • Official Title: A Phase 1b Trial of a Combination of mFOLFIRI With MEK162 in Patients With Advanced KRAS Positive Metastatic Colorectal Cancers

Clinical Trial IDs

  • ORG STUDY ID: HCI87144
  • NCT ID: NCT02613650

Conditions

  • Advanced KRAS Positive Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
MEK162 and mFOLFIRIBinimetinibMEK162 and mFOLFIRI, all patients

Purpose

This is a Phase 1b, open label, dose-finding study to determine the Maximum Tolerated Dose (MTD) of MEK162 in combination with mFOLFIRI, and to evaluate the response rate, clinical benefit rate and additional safety parameters of the treatment combination

Trial Arms

NameTypeDescriptionInterventions
MEK162 and mFOLFIRI, all patientsExperimental
  • MEK162 and mFOLFIRI

Eligibility Criteria

        Inclusion Criteria:

          -  Age > 18 years old

          -  Patients with histologically confirmed KRAS positive metastatic colorectal cancer.

          -  Patients must have progressed during or after first-line treatment for metastatic
             disease with oxaliplatin and fluoropyrimidines based chemotherapy (with failure within
             six months) or not be a candidate for oxaliplatin (i.e. neuropathy).

          -  ECOG Performance Status 0-1

          -  Able to provide informed consent and willing to sign an approved consent form that
             conforms to federal and institutional guidelines.

          -  Women of childbearing potential must have a negative blood pregnancy test at the
             screening visit

          -  Adequate bone marrow, organ function and laboratory parameters as defined by the
             protocol

          -  Adequate cardiac function as defined by the protocol

          -  Must have recovered from adverse effects of any prior surgery, radiotherapy or other
             antineoplastic therapy. Alopecia and CTCAE grade 1 peripheral neuropathy is acceptable

          -  Willingness and ability to comply with all study procedures and able to take oral
             medications

        Dose Expansion Phase Additional Inclusion Criteria

          -  Patients must be willing and able to undergo biopsy according to the institute's own
             guidelines and requirements for such procedures

          -  Patients must have measurable disease as defined by RECIST v1.1 (at least one lesion ≥
             10mm in at least one dimension when assessed by CT or MRI, or a cutaneous lesion with
             clearly defined margins that measures ≥ 10 mm in at least one dimension)

          -  Patients must be irinotecan refractory. Patients must have progressed on prior
             irinotecan therapy but must be able to tolerate standard irinotecan doses.

        Exclusion Criteria:

          -  UGT1A1 *28 homozygous patients

          -  Previous treatment with any MEK inhibitor

          -  Treatment with systemic antineoplastic therapy (including unconjugated therapeutic
             antibodies and toxin immunoconjugates) or any investigational therapy within 4 weeks
             (<6 weeks for nitrosurea or mitomycin-C, antibodies except for trastuzumab) or within
             5-half lives of the investigational therapy prior to starting study treatment,
             whichever is longer

          -  Patient received radiotherapy within 2 weeks prior to the first dose of study
             treatment except localized radiation therapy for symptomatic bone metastasis.

          -  Have had a diagnosis of another malignancy, unless the patient has been disease-free
             for at least 3 years following the completion of curative intent therapy, with the
             following exceptions:

               -  Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical
                  intraepithelial neoplasia, regardless of the disease-free duration, are eligible
                  for this study if definitive treatment for the condition has been completed.

               -  Patients with organ-confined prostate cancer with no evidence of recurrent or
                  progressive disease based on prostate-specific antigen (PSA) values are also
                  eligible for this study if hormonal therapy has been initiated or a radical
                  prostatectomy has been performed.

          -  History or current evidence of retinal vein occlusion (RVO) or current risk factors
             for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity
             or hypercoagulability syndromes.

          -  Personal history of Gilbert's syndrome.

          -  Uncontrolled arterial hypertension defined by blood pressure >150 mmHg systolic and/or
             100 mmHg diastolic at rest (average 3 consecutive readings at least 5 minutes apart)
             despite appropriate medical therapy.

          -  Impaired cardiovascular function or clinically significant cardiovascular diseases,
             including any of the following:

               -  History of acute coronary syndromes (including myocardial infarction, unstable
                  angina, coronary artery bypass grafting, coronary angioplasty, or stenting) <6
                  months prior to screening,

               -  Symptomatic chronic heart failure; evidence of clinically significant cardiac
                  arrhythmias and/or conduction abnormalities < 6 months prior to screening except
                  atrial fibrillation and paroxysmal supraventricular tachycardia.

          -  Known positive serology for HIV, active Hepatitis B, and/or active Hepatitis C
             infection (Note: if not suspected, testing is not required at baseline).

          -  Patients who have neuromuscular disorders that are associated with elevated CK (e.g.,
             inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal
             muscular atrophy).

          -  Patients who are planning on embarking on a new strenuous exercise regimen after first
             dose of study treatment. Muscular activities, such as strenuous exercise, that can
             result in significant increases in plasma CK levels should be avoided while on MEK162
             treatment.

          -  Impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative
             disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small
             bowel resection that under the judgment of the PI may impair absorption of study
             drugs).

          -  Any other condition that would, in the Investigator's judgment, contraindicate the
             patient's participation in the clinical study due to safety concerns or compliance
             with clinical study procedures, e.g., infection/inflammation, intestinal obstruction,
             unable to swallow medication.(patients may not receive drug through a feeding tube),
             social/ psychological issues, etc.

          -  Patients who have undergone major surgery ≤ 3 weeks prior to starting study drug or
             who have not recovered from side effects of such procedure.

          -  Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
             female after conception and until the termination of gestation, confirmed by a
             positive hCG laboratory test.

          -  Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, unless they are using highly effective methods of contraception
             throughout the study and for 15 days after study drug discontinuation.

          -  Sexually active males unless they use a condom during intercourse while taking the
             drug and for 15 days after stopping treatment and should not father a child in this
             period. A condom is required to be used also by vasectomized men in order to prevent
             delivery of the drug via seminal fluid.

          -  Medical, psychiatric, cognitive or other conditions that may compromise the patient's
             ability to understand the patient information, give informed consent, comply with the
             study protocol or complete the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities (DLTs) of combination MEK162 and mFOLFIRI
Time Frame:Patient safety will be evaluated throughout the treatment period (treatment with MEK162 and mFOLFIRI which is expected to last 6-10 months for each patient)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Utah

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