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

Phase 2
Completed
Conditions
Colorectal Cancer
KRAS Wildtype
NRAS Wildtype
BRAF Wildtype
Interventions
Registration Number
NCT02399943
Lead Sponsor
University Health Network, Toronto
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
14
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Trametinib and PanitumumabTrametinibTrametinib: 2 mg QD, orally, continuously. Panitumumab: 6 mg/kg, intravenously, Q2W
Trametinib and PanitumumabPanitumumabTrametinib: 2 mg QD, orally, continuously. Panitumumab: 6 mg/kg, intravenously, Q2W
Primary Outcome Measures
NameTimeMethod
Percentage of patients who experience complete response, partial response, or stable disease24 weeks

by RECIST 1.1 criteria

Secondary Outcome Measures
NameTimeMethod
Frequency and proportion of patients who experience side effects.3 years

by system organ class and preferred term

Time period from the first dose of Trametinib and Panitumumab to the first date in which progression or death is observed3 years
Date of first confirmed response to the first date in which progression is observed3 years
Proportion of subjects achieving either a complete or partial tumor response3 years

by RECIST 1.1 criteria

Trial Locations

Locations (1)

Princess Margaret Cancer Centre

🇨🇦

Toronto, Ontario, Canada

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