Clinical trial NCT02399943: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
KRAS Wildtype
NRAS Wildtype
BRAF Wildtype
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2015-03-26
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of patients who experience complete response, partial response, or stable disease
timeFrame: 24 weeks
Secondary outcomes:
measure: Frequency and proportion of patients who experience side effects.
timeFrame: 3 years
measure: Proportion of subjects achieving either a complete or partial tumor response
timeFrame: 3 years
measure: Time period from the first dose of Trametinib and Panitumumab to the first date in which progression or death is observed
timeFrame: 3 years
measure: Date of first confirmed response to the first date in which progression is observed
timeFrame: 3 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Philippe Bedard, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alshammari K, Aung KL, Zhang T, Razak ARA, Serra S, Stockley T, Wang L, Nguyen J, Spreafico A, Hansen AR, Zwir D, Siu LL, Bedard PL. Phase II Trial of Trametinib and Panitumumab in RAS/RAF Wild Type Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2021 Dec;20(4):334-341. doi: 10.1016/j.clcc.2021.07.004. Epub 2021 Jul 24.