Clinical Trials /

A Trial of Trametinib and Panitumumab in RAS/RAF Wild Type Advanced Colorectal Cancer

NCT02399943

Description:

This is a phase 2 study (the second phase in testing a new drug or drug combination) to see how useful the combination of two drugs, panitumumab and trametinib, are in patients with advanced colorectal cancer with KRAS, NRAS, or BRAF wild type (genes that are not mutated). Panitumumab is a drug that is approved by Health Canada for the treatment of advanced colorectal cancer with KRAS wild type. Panitumumab works by binding to and blocking the protein, epidermal growth factor receptor (EGFR) from working. Trametinib is a drug that is approved by Health Canada for the treatment of melanoma with a mutation in the BRAF gene. Trametinib works by binding to and blocking mitogen-activated protein kinase kinase (MEK) 1 and MEK2 from working. Previous studies have shown that the combination of panitumumab and trametinib may be more useful in KRAS, NRAS, or BRAF wild type colorectal cancer.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Trial of Trametinib and Panitumumab in RAS/RAF Wild Type Advanced Colorectal Cancer
  • Official Title: Molecular Basket Trial In Multiple Malignancies With Common Target Pathway Aberrancies

Clinical Trial IDs

  • ORG STUDY ID: MOBILITY-001
  • NCT ID: NCT02399943

Conditions

  • Colorectal Cancer
  • KRAS Wildtype
  • NRAS Wildtype
  • BRAF Wildtype

Interventions

DrugSynonymsArms
TrametinibMEKINISTTrametinib and Panitumumab
PanitumumabVECTIBIXTrametinib and Panitumumab

Purpose

This is a phase 2 study (the second phase in testing a new drug or drug combination) to see how useful the combination of two drugs, panitumumab and trametinib, are in patients with advanced colorectal cancer with KRAS, NRAS, or BRAF wild type (genes that are not mutated). Panitumumab is a drug that is approved by Health Canada for the treatment of advanced colorectal cancer with KRAS wild type. Panitumumab works by binding to and blocking the protein, epidermal growth factor receptor (EGFR) from working. Trametinib is a drug that is approved by Health Canada for the treatment of melanoma with a mutation in the BRAF gene. Trametinib works by binding to and blocking mitogen-activated protein kinase kinase (MEK) 1 and MEK2 from working. Previous studies have shown that the combination of panitumumab and trametinib may be more useful in KRAS, NRAS, or BRAF wild type colorectal cancer.

Trial Arms

NameTypeDescriptionInterventions
Trametinib and PanitumumabExperimentalTrametinib: 2 mg QD, orally, continuously. Panitumumab: 6 mg/kg, intravenously, Q2W
  • Trametinib
  • Panitumumab

Eligibility Criteria

        Inclusion Criteria:

          -  18 years of age or older

          -  KRAS/NRAS/BRAF wild type colorectal cancer, not responsive to standard therapies, no
             approved or curative therapy, refuse standard therapy

          -  Prior 5-FU, oxaliplatin and irinotecan

          -  ECOG Performance Status of 0 or 1

          -  Able to swallow/retain oral drugs

          -  Able and agree to have provide tumor tissue/have biopsies

          -  Agree to use contraception

          -  Not pregnant

          -  Adequate organ system function

        Exclusion Criteria:

          -  Chemotherapy, radiotherapy, immunotherapy, or other anti-cancer therapies <28 days or
             5 half lives

          -  Prior EGFR, MEK, or RAF inhibitor or regorafenib

          -  Current use of prohibited medications

          -  Unresolved side effects

          -  GI disease or other condition affecting GI absorption

          -  Mucosal or internal bleeding

          -  Any major surgery <four weeks

          -  HIV, HBV, or HCV positive

          -  Active infection

          -  Leptomeningeal disease

          -  Brain metastases

          -  Unacceptable QTcF interval

          -  Significant uncontrolled arrhythmias

          -  Acute coronary syndromes, myocardial infarction, coronary angioplasty, or stenting or
             bypass grafting < 6 mos.

          -  Class II, III, or IV heart failure

          -  Other clinically significant ECGs

          -  Intra - cardiac defibrillators

          -  Cardiac metastases

          -  Condition that may interfere with patient safety

          -  Hypersensitivity to study drugs

          -  Severe or uncontrolled systemic diseases

          -  Pregnant or lactating

          -  Retinal vein occlusion

          -  Interstitial lung disease or pneumonitis

          -  Active liver or biliary disease
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of patients who experience complete response, partial response, or stable disease
Time Frame:24 weeks
Safety Issue:
Description:by RECIST 1.1 criteria

Secondary Outcome Measures

Measure:Frequency and proportion of patients who experience side effects.
Time Frame:3 years
Safety Issue:
Description:by system organ class and preferred term
Measure:Proportion of subjects achieving either a complete or partial tumor response
Time Frame:3 years
Safety Issue:
Description:by RECIST 1.1 criteria
Measure:Time period from the first dose of Trametinib and Panitumumab to the first date in which progression or death is observed
Time Frame:3 years
Safety Issue:
Description:
Measure:Date of first confirmed response to the first date in which progression is observed
Time Frame:3 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University Health Network, Toronto

Last Updated

February 2, 2018