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

Colorectal Cancer Clinical Trial

Official title:

Molecular Basket Trial In Multiple Malignancies With Common Target Pathway Aberrancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02399943
• Other study ID #: MOBILITY-001
• Status: Completed
• Phase: Phase 2
• Start date: June 2015
• Est. completion date: March 31, 2022

Study information

• Verified date: May 2022
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: March 31, 2022
• Est. primary completion date: April 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Trametinib

• Panitumumab

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients who experience complete response, partial response, or stable disease	by RECIST 1.1 criteria	24 weeks
Secondary	Frequency and proportion of patients who experience side effects.	by system organ class and preferred term	3 years
Secondary	Proportion of subjects achieving either a complete or partial tumor response	by RECIST 1.1 criteria	3 years
Secondary	Time period from the first dose of Trametinib and Panitumumab to the first date in which progression or death is observed		3 years
Secondary	Date of first confirmed response to the first date in which progression is observed		3 years