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.
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
Drug | Synonyms | Arms |
---|
Trametinib | MEKINIST | Trametinib and Panitumumab |
Panitumumab | VECTIBIX | Trametinib 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
Name | Type | Description | Interventions |
---|
Trametinib and Panitumumab | Experimental | Trametinib: 2 mg QD, orally, continuously.
Panitumumab: 6 mg/kg, intravenously, Q2W | |
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: | Active, not recruiting |
Lead Sponsor: | University Health Network, Toronto |
Last Updated
February 26, 2021